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OverviewAetiologyPathophysiologyClinical features and red flagsInvestigationsDifferential diagnosisManagementComplicationsMonitoring and follow-upSpecial situationsCommon pitfallsQuestionsSources
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Educational draft · awaiting clinical reviewThe full textbook explains uncertainty but does not replace live national or local guidance, specialist advice, or current prescribing information.

Skeletal metastases and pathological fracture

Musculoskeletal medicine and orthopaedics · UK scope · Sources checked 27 Aug 2026 · Clinical review pending

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Time-critical presentation

Use ABCDE for major pathological fracture, give prompt analgesia, splint the limb, document skin and distal neurovascular function and protect weight bearing. New weakness, sensory level, gait change or bladder or bowel dysfunction activates the metastatic spinal cord-compression pathway immediately. Treat severe symptomatic hypercalcaemia, haemorrhage, sepsis and threatened skin urgently. A solitary uncharacterised lesion is not automatically a metastasis: obtain tumour-aware specialist advice before biopsy or definitive fixation.

Overview

Recognise mechanically unstable metastatic bone disease, establish diagnosis before contaminating surgery and construct a coordinated stabilisation, radiotherapy and systemic-treatment plan that restores useful function.

Define the mechanical problem before reviewing the cancer history. Ask about pain at rest, at night and specifically during standing, turning in bed, transfers and limb rotation. Establish sudden change, ability to bear weight, previous radiotherapy, systemic treatment, known histology and current disease control. Record prognosis-relevant performance, comorbidity, pre-morbid mobility and goals. A patient with stable visceral disease may need a more durable reconstruction than an apparently similar radiograph in the final weeks of life.

Examine the whole limb and adjacent joints, looking for deformity, swelling, threatened skin and previous scars. Palpate gently, avoiding provocative torsion through a lytic femur. Document pulses, capillary refill and motor and sensory function. Assess hydration and cognition for hypercalcaemia and examine the spine neurologically whenever back pain, gait change or sphincter symptoms occur. Splint a completed fracture and use a frame or crutches for an impending lesion.

Practice

Two practice questions

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Musculoskeletal medicine and orthopaedicsOriginal SBA

Solitary lesion before fixation

An adult without a confirmed cancer diagnosis has a solitary destructive femoral lesion and a minimally displaced pathological fracture. What should precede definitive internal fixation?

Choose one answer, then submit
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Sources and review status5 sources · checked 27 Aug 2026 · clinical review pending+
Sources

Sources and review status

National guidance is shown before implementation-dependent detail. Typical adult dose examples remain subject to patient factors, contraindications and the live BNF or specialist protocol. Source check completed 27 Aug 2026; clinical approval remains outstanding.

  • Long-Bone Metastasis Management ReviewMechanical assessment, prophylactic fixation and radiotherapy coordination.
  • NICE NG234 Spinal Metastases and MSCCEmergency neurological recognition, imaging and definitive care.
  • NICE TA265 Denosumab for Bone MetastasesNHS eligibility for prevention of skeletal-related events.
  • Zoledronic Acid 4 mg SmPCCancer dosing, infusion, renal modification and mineral safety.
  • Xgeva Summary of Product CharacteristicsDenosumab cancer regimen, hypocalcaemia and dental precautions.

Editorial contact: Doctor’s Passport editorial team. Source-check date is separate from clinical approval. Report a content problem · Content changes

Authoring stateComplete draftClinical stateAwaiting reviewJurisdictionUnited Kingdom
Radiograph the entire symptomatic bone in two planes because a narrow image can miss a second lesion or exclude the joint needed for reconstruction. Identify lytic, blastic or mixed pattern, lesion length, cortical circumference, fracture line and periarticular involvement. CT shows cortical windows, pelvic geometry and cement or implant planning. MRI detects occult marrow disease, extraosseous extent and fracture and is mandatory for neurological spinal questions. Stage the remainder of skeleton according to primary-cancer biology and management purpose.

Do not confuse probable with proven histology. In a patient with widespread documented breast or prostate cancer and multiple concordant lesions, tissue may add little. A solitary deposit, no known primary, long disease-free interval or unusual imaging needs staging and biopsy before definitive surgery. Complete CT chest, abdomen and pelvis and primary-specific tests as directed. The biopsy tract is planned by the treating orthopaedic oncology team, especially when primary bone sarcoma remains in the differential.

Assess mechanical risk through symptoms and anatomy rather than a single score. Mirels combines site, pain, lesion type and size and can support communication, but its intermediate range is imprecise and it must not override CT cortical assessment or specialist judgement. Functional pain and extensive cortical destruction in the peritrochanteric femur carry particular concern. Protect loading while the multidisciplinary team chooses prophylactic fixation, radiotherapy or observation.

For a completed long-bone fracture, reconstruction should permit early function and avoid reliance on biological union through tumour. Intramedullary fixation spans an appropriate segment and can be reinforced with cement; endoprosthetic replacement bypasses extensive periarticular or proximal femoral destruction. Plate constructs may suit selected anatomical sites. Estimate survival using disease, visceral burden, treatment options and performance without denying durable surgery solely because cancer is metastatic.

Coordinate local and systemic control. Post-fixation radiotherapy is commonly planned after wound recovery to reduce progression around hardware. Uncomplicated painful lesions not at immediate fracture risk often respond to external-beam radiotherapy, including a single 8 Gy fraction in many palliative settings. Systemic endocrine, cytotoxic, targeted, immune or radiopharmaceutical therapy follows tumour biology. Consider embolisation before surgery for hypervascular renal or thyroid deposits after specialist angiographic review.

Bone-modifying agents reduce skeletal-related events in selected cancers. Zoledronic acid requires creatinine-based dosing and calcium monitoring; denosumab avoids renal dose adjustment but can cause profound hypocalcaemia in kidney disease. Both need oral-health assessment and calcium and vitamin-D provision where appropriate. Rehabilitation begins early with explicit loading, pain, thrombosis and falls plans. Monitor the entire construct and patient, because disease progression, not callus, often determines long-term stability.

Key points

  • Deep progressive pain is common, but functional pain with standing, transfers or limb rotation is the high-yield sign of mechanical instability.
  • First-line imaging of a symptomatic peripheral bone is radiography in two planes including the whole lesion and adjacent joint; a normal film does not exclude marrow disease.
  • CT defines cortical destruction and fixation anatomy, while MRI is the reference study for marrow, occult fracture, soft tissue and neural involvement.
  • Protect weight bearing immediately across a painful proximal femoral or other high-load lesion until specialist assessment determines fracture risk.
  • Before biopsy or fixation, establish whether histology is already secure; stage and sample a solitary or atypical lesion because primary sarcoma remains possible.
  • Surgery aims for immediate durable stability, usually using load-sharing fixation, cement augmentation or endoprosthetic replacement chosen to survive the patient's expected lifespan.
  • Postoperative radiotherapy improves local control for many stabilised metastatic lesions, but radiotherapy alone cannot immediately restore a critically weakened cortex.
  • Tumour-specific systemic therapy and zoledronic acid or denosumab can reduce later skeletal events but do not replace analgesia, fracture protection, decompression or fixation.

Aetiology

01

Common epithelial primaries

Breast, prostate, lung, kidney and thyroid cancers frequently spread to bone, but almost any advanced malignancy can produce skeletal deposits.

02

Haematological malignancy

Myeloma and lymphoma can weaken bone through marrow and cortical disease and require different systemic therapy and biopsy handling from carcinoma metastasis.

03

Unknown primary presentation

Bone pain or fracture may precede recognition of the cancer, making staged investigation essential before assuming histology from age or radiographic appearance.

04

Treatment-altered skeleton

Radiotherapy, endocrine therapy, corticosteroids, disuse and previous implants can compound fragility around a metastatic focus and influence reconstruction.

Pathophysiology

  1. 1
    Haematogenous marrow seeding

    Tumour cells lodge in vascular red marrow, especially spine, pelvis and proximal long bones, then interact with stromal and bone-remodelling pathways.

  2. 2
    Osteolytic destruction

    Tumour-stimulated osteoclast activity removes trabecular and cortical bone, producing functional pain, hypercalcaemia and rapid mechanical weakening.

  3. 3
    Osteoblastic response

    Prostate and some breast metastases drive disorganised new bone that appears sclerotic but can remain brittle and conceal interspersed lytic weakness.

  4. 4
    Cortical load failure

    As tumour erodes the load-bearing circumference, ordinary bending and torsion concentrate through residual cortex until an impending lesion becomes a complete fracture.

  5. 5
    Epidural and vertebral collapse

    Posterior vertebral extension or pathological collapse narrows the canal, threatening cord or cauda-equina function independently of systemic cancer burden.

Clinical features and red flags

Functional weight-bearing pain

Pain reliably triggered by standing, transfer or limb rotation indicates structural insufficiency and predicts failure better than night pain alone.

Lytic cortical loss

Destruction extending through a substantial circumference, especially in proximal femur, removes bending and torsional reserve.

Blastic but fragile bone

Diffuse sclerosis can still contain disorganised weak matrix and does not guarantee safe loading or secure screw purchase.

Completed pathological fracture

Minimal-force deformity, crepitus and inability to use the limb through a lesion demands splintage and urgent reconstruction assessment.

Unknown-primary discordance

A solitary lesion or unusual phenotype without confirmed cancer histology must be staged and sampled before treatment assumption.

Hypervascular metastasis

Renal or thyroid origin, intense enhancement and prominent vessels warn of potentially major haemorrhage during biopsy or fixation.

Red flags requiring action

  • Functional pain on standing or transfers through a proximal femoral lesion indicates mechanical failure risk even before a visible fracture line.
  • A painful deformed limb after minimal force is a completed pathological fracture requiring splintage and urgent orthopaedic oncology review.
  • Night spinal pain, radicular symptoms, weakness, gait deterioration or sphincter change may be metastatic cord or cauda-equina compression.
  • A solitary destructive lesion with no secure primary diagnosis could be sarcoma, myeloma or infection and must not undergo empirical intramedullary fixation.
  • Renal-cell and thyroid metastases may be markedly vascular, creating major biopsy and operative bleeding risk that sometimes warrants preoperative embolisation.
  • Confusion, dehydration, vomiting, constipation or arrhythmia with extensive lytic disease suggests hypercalcaemia requiring urgent biochemical treatment.

Investigations

  1. 01
    First-line whole-bone radiographsFirst stepFirst line
    Why
    Define fracture, lesion phenotype, cortical loss, joint involvement and other deposits along the proposed construct.
    Interpretation and limitations
    Two planes are essential; functional pain with a normal radiograph may still need MRI for occult marrow or stress injury.
  2. 02
    CT for cortical and operative mapping
    Why
    Quantify residual cortex, pelvic or periarticular anatomy and the bone available for fixation or replacement.
    Interpretation and limitations
    Axial cortical involvement refines mechanical judgement beyond Mirels and can identify a lesion that radiation alone will not stabilise.
  3. 03
    MRI for marrow and neural extent
    Why
    Detect occult fracture, soft-tissue extension and neurovascular or spinal-canal involvement.
    Interpretation and limitations
    MRI is the reference for suspected cord compression and should cover the whole spine within the emergency timeframe when neurological symptoms exist.
  4. 04
    Systemic staging and myeloma screen
    Why
    Identify primary cancer, visceral burden, other skeletal lesions and a plasma-cell alternative before biopsy or surgery.
    Interpretation and limitations
    Select CT, bone scan, PET-CT, whole-body MRI and laboratory testing according to clinical context and suspected biology.
  5. 05
    Specialist-planned core biopsy
    Why
    Confirm histology in a solitary, atypical or management-changing lesion before definitive fixation.
    Interpretation and limitations
    Obtain tissue after staging through a tract compatible with resection; send microbiology as well as pathology when infection remains possible.

Differential diagnosis

01

Primary bone sarcoma

A solitary aggressive lesion, particularly without confirmed carcinoma, requires sarcoma-centre planning because an unplanned nail can destroy curative local options.

02

Multiple myeloma

Anaemia, renal impairment, hypercalcaemia, monoclonal protein and punched-out lesions support plasma-cell disease with a distinct systemic and skeletal pathway.

03

Osteomyelitis

Fever, inflammatory response, sinus or abscess suggests infection, although tissue should be sent for both microbiology and histology when uncertainty remains.

04

Insufficiency fracture

Osteoporosis, radiotherapy or antiresorptive-associated stress failure can fracture bone without a tumour focus and changes operative and oncological treatment.

05

Benign bone lesion

A cyst, enchondroma or fibrous dysplasia may fracture, but adult pain and destructive change require specialist confirmation rather than benign assumption.

Management

01ImmediateProtect the failing skeletonFirst stepFunctional pain, cortical destruction or a complete fracture threatens safe limb use.+
  1. 1Stop unprotected loading, splint a completed fracture and document skin, pulses and neurological function.
  2. 2Provide multimodal analgesia and assess bleeding, calcium, renal function, VTE and pressure-area risk.
  3. 3Obtain whole-bone radiographs and urgent CT or MRI according to cortical, occult-fracture or neural questions.
  4. 4Contact orthopaedic oncology early rather than waiting for routine radiotherapy review.
02DiagnosisProve atypical or solitary diseaseHistology is unknown, the lesion is solitary or imaging is discordant with the established primary.+
  1. 1Complete systemic staging and review all previous cancer pathology and imaging.
  2. 2Keep sarcoma, myeloma and infection in the differential and avoid empirical internal fixation.
  3. 3Arrange tumour-team-planned core biopsy through a tract compatible with subsequent surgery.
  4. 4Agree the treatment sequence only after radiology, pathology and oncology findings are concordant.
03ReconstructionBuild for immediate durable functionA fracture or high-risk lesion is unlikely to remain mechanically safe with non-operative care.+
  1. 1Select prophylactic fixation, cemented load-sharing construction or endoprosthetic replacement from site, bone loss and prognosis.
  2. 2Span disease appropriately and assume limited biological union when deciding construct strength.
  3. 3Consider preoperative embolisation for hypervascular metastasis and coordinate blood, thrombosis and anaesthetic planning.
  4. 4Mobilise to the prescribed load early and arrange postoperative radiotherapy after wound review.
04Non-operative local controlTreat pain without ignoring mechanicsThe lesion is painful but structurally stable or surgery offers no proportionate benefit.+
  1. 1Provide explicit loading guidance, aids and multimodal analgesia rather than generic activity as tolerated.
  2. 2Use palliative external-beam radiotherapy for local pain and tumour control according to oncology planning.
  3. 3Start or optimise tumour-specific systemic treatment and eligible bone-modifying therapy.
  4. 4Reassess urgently for increasing functional pain or radiographic cortical loss because stability can change during treatment.
Key medicines and prescribing safety3 treatments · regimens, roles and cautions+
Reduces later pathological fracture, spinal compression and need for skeletal radiotherapy or surgery in selected advanced malignancies.

Zoledronic acid for eligible bone metastases

Use 4 mg by intravenous infusion over at least 15 minutes every three to four weeks for licensed skeletal-event prevention, modifying dose for baseline renal function according to the product information.

Check creatinine before each dose, correct hypocalcaemia, provide calcium and vitamin D when appropriate and complete preventive dental assessment because renal injury and jaw osteonecrosis can occur.

Reduces skeletal-related events for defined adults with bone metastases from solid tumours when selected by oncology.

Denosumab for eligible solid-tumour bone disease

Administer 120 mg subcutaneously once every four weeks with calcium and vitamin-D supplementation unless hypercalcaemia prevents it, following NICE eligibility and product guidance.

Correct calcium first and monitor closely in severe renal impairment; review oral health, jaw symptoms and pregnancy prevention and do not confuse this schedule with osteoporosis dosing.

Controls severe movement and rest pain during splintage, transfers and definitive stabilisation planning.

Immediate-release morphine for severe fracture pain

Titrate an individual short-acting oral dose under local acute-pain or palliative guidance, starting lower in frailty and renal impairment and prescribing bowel and nausea prophylaxis.

Monitor sedation, respiratory rate, delirium and constipation; escalating requirement may signal fracture progression, compartment pressure or cord compression rather than tolerance alone.

Complications

01

Complete pathological fracture

Failure causes severe pain, bleeding, immobility and a substantially more difficult reconstruction than planned prophylactic stabilisation surgery.

02

Metastatic cord compression

Neurological impairment can become irreversible without immediate corticosteroid, whole-spine MRI and definitive surgical decompression or radiotherapy decisions.

03

Hypercalcaemia and renal injury

Accelerated resorption causes dehydration, neurocognitive change and arrhythmia, while nephrotoxic treatment and obstruction may compound kidney dysfunction.

04

Implant or construct failure

Progressive tumour, non-union and insufficient fixation length can break hardware unless reconstruction is designed to outlast expected survival.

05

Loss of mobility

Pain, fear and prolonged non-weight-bearing rapidly cause sarcopenia, thrombosis, pressure injury and loss of independence even when cancer is otherwise treatable.

Monitoring and follow-up

  • Reassess functional pain, transfer safety, limb alignment, skin and distal neurovascular findings while a lesion awaits treatment.
  • Track exact loading instructions and mobility aids across ward, radiotherapy and community handovers to avoid accidental fracture completion.
  • After surgery, monitor wound, haemoglobin, VTE, implant alignment and early function before coordinating local radiotherapy.
  • Review renal function, adjusted calcium, phosphate, magnesium and dental symptoms during repeated bone-modifying treatment.
  • Repeat imaging for new or worsening mechanical pain, because radiation response does not prove cortical strength has recovered.
  • Match surveillance and construct durability to updated systemic response, performance and goals through multidisciplinary review.

Special situations

Pain can be a load test

Pain during standing or rotation reveals mechanical insufficiency that a static radiograph or generic pain score can underestimate.

Metastasis still needs histology

A known cancer does not explain every solitary bone lesion, particularly after a long remission or with discordant imaging.

Radiation is not internal fixation

Tumour response develops over time and cannot immediately replace cortex that is already close to failure.

Union may never carry load

Metastatic reconstruction is designed for immediate construct stability because irradiated or tumour-filled bone may not heal normally.

Sclerosis can deceive

Blastic tumour produces dense-looking but mechanically abnormal bone, so symptoms and cortex remain important.

Durability follows prognosis

Longer survival supports a reconstruction resistant to progression and hardware fatigue, not a less ambitious operation because cancer is present.

Common pitfalls

  1. 01

    Referring a functionally painful proximal femoral lesion for radiotherapy without orthopaedic mechanical assessment.

  2. 02

    Using a Mirels total as the sole rule while ignoring CT cortical destruction, pain trajectory and tumour biology.

  3. 03

    Fixing a solitary unbiopsied lesion and later discovering that it was a primary bone sarcoma.

  4. 04

    Imaging only the fracture site rather than the full bone and adjacent joint required for reconstruction.

  5. 05

    Choosing a construct that depends on union or cannot outlast the patient's realistic survival.

  6. 06

    Allowing unclear activity as tolerated instructions to persist across transfer, radiotherapy and community rehabilitation.