01OverviewDefinition, clinical context and the essential points that orientate the chapter.
Metastatic bone disease disrupts a continuously remodelled organ. Some cancers stimulate osteoclasts and appear lytic, some stimulate disorganised osteoblasts and appear sclerotic, and many are mixed. Neither a dense lesion nor a small radiographic footprint guarantees strength. The practical questions are whether pain is tumour related, whether bone is about to fail, whether neural tissue is threatened and whether the lesion truly represents the known cancer.
Imaging is question driven. Plain radiographs show gross cortical loss and fracture in a painful limb. CT defines three-dimensional cortical and vertebral anatomy. MRI detects marrow replacement, soft-tissue extension, occult fracture and epidural disease. A nuclear bone scan maps osteoblast reaction but underperforms in purely lytic lesions and myeloma. PET tracer selection follows tumour biology. If a lesion is solitary or discordant, obtain tissue through a route agreed with the surgeon because a primary sarcoma remains in the differential until proved otherwise.
Local management separates biological pain from mechanical instability. External-beam radiotherapy relieves uncomplicated metastatic pain, commonly with a single 8 Gy fraction. A weakened femur that hurts on weight bearing may fracture before radiation works and should be stabilised prophylactically when risk is high. Spinal disease requires assessment of neurological compression and mechanical instability; selected patients benefit from decompression and stabilisation followed by radiotherapy, while others receive urgent radiation alone.
Bone-modifying treatment suppresses osteoclast activity and delays fracture, cord compression, radiotherapy or surgery to bone in selected populations. Zoledronic acid requires renal monitoring; denosumab does not require renal dose adjustment but causes more hypocalcaemia when kidney function is poor. Both carry osteonecrosis-of-jaw risk, so dental prevention and symptom reporting matter. Treatment duration and interval are individualised around cancer type, response, renal and dental risk, prognosis and current commissioning rather than continued automatically forever.
Key points
- Bone metastases most often involve spine, pelvis, ribs and proximal long bones and arise commonly from breast, prostate, lung, renal and thyroid cancers.
- Deep progressive night pain is typical; movement- or weight-bearing pain suggests mechanical instability and may precede a pathological fracture.
- First-line assessment of a focal symptomatic peripheral site is plain radiography in two planes, but a normal film does not exclude early marrow metastasis.
- CT best defines cortical destruction and supports operative or radiotherapy planning; MRI is preferred for marrow, soft tissue, neural anatomy and occult fracture.
- Whole-spine MRI is the diagnostic reference standard for suspected metastatic spinal cord compression and must be arranged within 24 hours through the emergency pathway.
- Bone scintigraphy surveys osteoblastic activity but can miss purely lytic or marrow disease; FDG PET-CT, PSMA PET-CT and whole-body MRI are selected by primary biology and purpose.
- Biopsy a solitary, atypical or management-changing lesion when the primary is unknown or imaging is discordant; plan the tract as if primary bone sarcoma remains possible.
- First-line treatment for uncomplicated painful bone metastasis is often palliative external-beam radiotherapy, with a single 8 Gy fraction providing effective pain relief for many adults.
- Radiotherapy does not stabilise an imminently failing long bone immediately. A high-risk lesion needs orthopaedic oncology assessment for prophylactic fixation before or integrated with radiation.
- For neurological metastatic cord compression, give dexamethasone 16 mg as soon as possible, protect movement if unstable and decide urgently between decompressive stabilisation and radiotherapy.
- Treat the underlying cancer with tumour-specific endocrine, cytotoxic, targeted, immune or radiopharmaceutical therapy; local skeletal care remains necessary while systemic response develops.
- Zoledronic acid or denosumab reduces skeletal-related events in defined cancer populations but does not replace analgesia, stabilisation, radiotherapy or anticancer treatment.
- Before repeated antiresorptive treatment, correct calcium and vitamin-D deficiency when appropriate, assess renal function for bisphosphonate and complete preventive dental review.
- Integrate multimodal analgesia, physiotherapy, falls prevention, walking aids, thrombosis prevention and rehabilitation so pain relief translates into useful function.
02AetiologyUnderlying causes, associations and risk factors, with why each one matters.
Common solid-tumour origins
Breast, prostate and lung cancers cause most skeletal metastases, while renal, thyroid and other tumours contribute distinctive lytic, vascular or mixed patterns.
Haematological bone disease
Myeloma produces osteoclast-dominant lytic lesions and marrow injury, requiring a separate clonal treatment pathway even when the presenting problem resembles epithelial bone metastasis.
Haematogenous dissemination
Tumour cells reach vascular red-marrow sites, especially vertebrae, pelvis, ribs, skull and proximal femora and humeri, then remodel the local skeletal niche.
Treatment-resistant sanctuary
Bone deposits can progress despite control elsewhere because tumour phenotype, drug penetration and the osteoblast–osteoclast microenvironment differ from the primary site.
03PathophysiologyThe causal sequence from the underlying abnormality to symptoms and harm.
- 1Osteolytic signalling
Tumour mediators increase RANK-ligand-driven osteoclast activity, releasing growth factors from matrix that feed further tumour growth and weaken cortical and trabecular bone.
- 2Osteoblastic signalling
Prostate and selected other cancers stimulate disorganised osteoblast activity; radiographic sclerosis may still contain structurally weak bone and active osteoclast turnover.
- 3Mechanical failure follows geometry
Fracture risk depends on lesion size, cortical destruction, anatomical load, pain and treatment sensitivity rather than the lytic or blastic label alone.
- 4Vertebral disease threatens neural tissue
Epidural extension, vertebral collapse and pathological fracture narrow the canal or destabilise the column, compressing cord or cauda equina and impairing perfusion.
- 5Calcium release can become systemic
Extensive osteolysis and tumour humoral signals overwhelm renal compensation, producing dehydration, acute kidney injury, neurological dysfunction and arrhythmia through hypercalcaemia.
04Clinical features and red flagsSymptoms, examination findings, patterns of presentation and time-critical warnings.
A deep localised ache that becomes constant, disturbs sleep and progresses despite ordinary analgesia suggests active marrow or cortical tumour.
Pain triggered by weight bearing, turning, sitting or limb use indicates reduced structural competence and should prompt load protection and stability assessment.
Sudden deformity or inability to bear weight is a completed fracture; escalating functional pain with major cortical loss may be an impending one.
Spinal pain with weakness, gait loss, sensory change or sphincter dysfunction requires emergency whole-spine MRI and immediate specialist treatment.
Thirst, polyuria, dehydration, constipation, vomiting, weakness, confusion or shortened QT can reflect tumour-driven calcium release and renal amplification.
Exposed jaw bone, dental non-healing, jaw pain or new bilateral thigh or groin ache raises osteonecrosis or atypical femoral stress injury.
05InvestigationsWhat to request, why it matters and how to interpret it.
Read from the initial assessment onwards. Tests may run in parallel in urgent care; first-line, preferred, confirmatory, definitive and gold-standard labels appear only when the chapter explicitly states them.
- 01
First-line two-plane radiographsFirst stepFirst line - Why
- Assess a symptomatic long bone or focal peripheral site for lysis, sclerosis, cortical loss, periosteal change and completed fracture.
- Interpretation and limitations
- Estimate the fraction and length of cortex involved and image the whole bone; early marrow deposits can be radiographically occult, so persistent symptoms proceed to MRI or CT.
- 02
CT for structural anatomy - Why
- Define cortical destruction, vertebral collapse, posterior-element disease and surgical or radiotherapy geometry and contribute to systemic staging.
- Interpretation and limitations
- CT strength assessment is anatomical rather than absolute; severe functional pain can signal instability even before a conventional fracture line appears.
- 03
Preferred MRI for marrow and neural diseasePreferred - Why
- Detect marrow replacement, soft-tissue extension, occult fracture and epidural, cord, cauda-equina or nerve-root compromise.
- Interpretation and limitations
- For suspected MSCC image the whole spine within 24 hours because symptoms can mislocalise and non-contiguous disease is common; use CT only when MRI is contraindicated.
- 04
Whole-skeleton functional imaging - Why
- Map additional disease with bone scintigraphy, FDG PET-CT, PSMA PET-CT or whole-body MRI according to primary tumour and decision.
- Interpretation and limitations
- A bone scan reflects osteoblast response and may be falsely quiet in lytic renal or thyroid lesions and myeloma; flare after effective therapy can mimic progression.
- 05
Reference biopsy for diagnostic uncertainty - Why
- Confirm metastatic lineage and obtain contemporary biomarkers when the primary is unknown, lesion solitary or pattern atypical.
- Interpretation and limitations
- Complete local imaging before core biopsy and agree a tract removable at any future operation; decalcification can damage molecular material, so coordinate specimen handling.
- 06
Laboratory and treatment baseline - Why
- Assess adjusted or ionised calcium, renal function, phosphate, magnesium, ALP, FBC and vitamin-D status before metabolic or bone-modifying treatment.
- Interpretation and limitations
- ALP can reflect osteoblastic burden but is non-specific; correct significant calcium and vitamin-D deficiency before antiresorptive treatment unless active hypercalcaemia changes supplementation.
06Differential diagnosisRealistic alternatives and the features that help distinguish them.
Primary bone tumour
A solitary aggressive lesion, unusual age or discordant cancer history requires sarcoma-centre imaging and biopsy planning before fixation because biopsy contamination changes definitive surgery.
Myeloma or lymphoma
Multifocal lytic disease, anaemia, renal impairment, raised total protein or marrow symptoms requires paraprotein, free-light-chain and haematological assessment rather than an assumed epithelial origin.
Osteomyelitis
Fever, raised inflammatory markers, adjacent ulcer or recent surgery supports infection, but culture and histology are needed when tumour and infection remain radiologically indistinguishable.
Osteoporosis and insufficiency fracture
Low-trauma vertebral or pelvic fractures can be benign, yet marrow replacement, posterior-element involvement, a soft-tissue mass or persistent progression raises malignant probability.
Degenerative or treatment-related pain
Facet, disc, osteoarthritis, avascular necrosis, neuropathy and radiation insufficiency injury remain common in cancer survivors and need anatomical correlation rather than automatic upstaging.
07ManagementImmediate care, first-line treatment, alternatives and escalation.
01New focal bone painSeparate uncomplicated pain from structural dangerFirst stepA patient with known or possible cancer develops persistent localised skeletal pain.+
- 1Examine tenderness, load-related pain, gait, limb function and full spinal neurology and ask explicitly about night pain, weakness and bladder or bowel change.
- 2Obtain site-appropriate radiographs and CT or MRI, protect weight bearing when failure is possible and stage the skeleton according to primary tumour biology.
- 3Biopsy a solitary or discordant lesion through a planned route, then combine systemic cancer treatment with radiotherapy, stabilisation, antiresorptive and rehabilitation decisions.
02Impending long-bone fractureStabilise before radiation when failure risk is highA lytic weight-bearing lesion causes functional pain, substantial cortical loss or a high formal fracture-risk score.+
- 1Stop unsafe weight bearing, provide appropriate analgesia and image the entire bone and adjacent joints, using CT when cortical geometry or surgical planning is uncertain.
- 2Refer urgently to orthopaedic oncology for prophylactic fixation or reconstruction before fracture, obtaining biopsy first when lineage is not secure.
- 3Give postoperative or coordinated palliative radiotherapy and systemic therapy, then restore gait and thrombosis prevention with physiotherapy and equipment support.
03Spinal neurological symptomsProtect cord function within hoursBack or radicular pain accompanies weakness, gait, sensory or sphincter change.+
- 1Contact the named MSCC service immediately, protect movement when instability is possible, document neurology and give dexamethasone 16 mg for neurological signs.
- 2DefinitiveObtain whole-spine MRI as soon as possible and within 24 hours, defining epidural compression, multiple levels and stability before definitive transfer.
- 3Choose urgent decompression and stabilisation for suitable patients or radiotherapy when surgery is unsuitable, then taper steroid and begin bladder, bowel, pressure and rehabilitation care.
04Longitudinal skeletal protectionReduce future events without creating dental or metabolic harmMetastatic bone disease is confirmed in a cancer population likely to benefit from a bone-modifying medicine.+
- 1Review cancer-specific evidence and funding, prognosis, renal function, calcium, phosphate, magnesium, vitamin D, dental health, previous antiresorptive exposure and planned dental procedures.
- 2Use zoledronic acid or denosumab at the licensed cancer schedule with calcium and vitamin-D support when appropriate and continue tumour-directed and local treatment.
- 3Reassess renal, calcium and jaw safety, new thigh pain, fracture events and ongoing benefit at defined intervals and pause or stop when harms or goals change.
Key medicines and prescribing safety3 treatments · regimens, roles and cautions+
Zoledronic acid for skeletal-event prevention
Give zoledronic acid 4 mg intravenously every 3 to 4 weeks in the licensed adult skeletal-event setting, modifying dose and withholding according to renal function and the current product protocol.Check creatinine, calcium, phosphate, magnesium, vitamin D and dental status; ensure hydration, infuse over at least 15 minutes and monitor acute-phase reaction, renal injury, hypocalcaemia and jaw osteonecrosis.
Denosumab for skeletal-event prevention
Give denosumab 120 mg subcutaneously once every 4 weeks for adults in the licensed and currently funded metastatic-bone population, with calcium and vitamin-D supplementation unless hypercalcaemia makes it inappropriate.Correct hypocalcaemia first and monitor closely in severe renal impairment; arrange preventive dentistry and watch jaw osteonecrosis, infection, atypical femoral fracture and rebound effects after stopping.
Dexamethasone for neurological MSCC
Give dexamethasone 16 mg orally immediately, or equivalent parenterally, when neurological symptoms or signs suggest MSCC, then continue 16 mg daily while surgery or radiotherapy is awaited and taper after definitive treatment starts.Monitor glucose, infection, mood, proximal weakness and gastrointestinal risk; stop if MSCC is excluded and seek specialist advice before steroid in unconfirmed lymphoma or myeloma without neurological signs.
08ComplicationsImportant consequences, why they occur and why they matter clinically.
Pathological fracture
Cortical and trabecular destruction causes painful collapse or long-bone failure, loss of mobility, bleeding, thrombosis and reduced ability to receive systemic treatment.
Metastatic spinal cord compression
Epidural tumour or vertebral instability can cause irreversible paralysis and bladder, bowel and sexual dysfunction; neurological status at treatment predicts recovery.
Malignant hypercalcaemia
Osteolytic and humoral mechanisms cause thirst, polyuria, dehydration, constipation, delirium, renal failure and rhythm disturbance requiring urgent metabolic treatment.
Marrow failure and pain crisis
Diffuse skeletal infiltration causes anaemia, thrombocytopenia, fatigue and bleeding while incident pain, immobility and escalating opioids impair cognition and independence.
Antiresorptive harm
Bisphosphonates and denosumab can cause hypocalcaemia and osteonecrosis of the jaw; renal injury affects bisphosphonate use and atypical femoral fracture occurs rarely.
09Monitoring and follow-upTreatment response, safety checks and longer-term review.
- Reassess pain at rest and during movement, analgesic toxicity, sleep, weight bearing, gait and daily function rather than recording a numerical pain score alone.
- Provide explicit same-day instructions for new weakness, numbness, gait decline, urinary retention or incontinence, saddle change and sudden inability to bear weight.
- After radiotherapy, review pain and analgesic need over weeks, recognise temporary pain flare and re-image persistent or mechanically worsening symptoms rather than repeating radiation blindly.
- After fixation or reconstruction, monitor wound, infection, thrombosis, implant integrity and rehabilitation and coordinate postoperative radiation and systemic treatment timing.
- Before and during zoledronic acid, check renal function and calcium-related biochemistry; during denosumab, prioritise calcium surveillance, especially with advanced kidney disease.
- Ask about dental pain, mobile teeth, exposed bone and planned extractions at every antiresorptive review and communicate cancer-dose exposure clearly to dental teams.
- Track systemic disease response, fracture and radiation events, mobility aids, falls, caregiver capacity and treatment goals to decide whether continued bone-modifying therapy adds value.
10Special situationsVariants, exceptions and circumstances that change the usual approach.
Sclerosis is not strength
Osteoblastic metastases contain disorganised bone and ongoing turnover, so prostate lesions can fracture or compress cord despite a dense radiograph.
Movement pain predicts mechanics
Pain on loading or turning points toward structural instability and may matter more immediately than size, tracer uptake or pain at rest.
Radiotherapy treats pain before strength
Tumour control and later recalcification take time; a femur likely to fail needs stabilisation rather than radiation as the only first step.
A bone scan sees the host response
Low osteoblast activity can hide aggressive lytic disease, while healing after treatment can increase uptake and imitate progression through flare.
The first biopsy must preserve options
A solitary destructive lesion may be primary sarcoma, so imaging and a resectable tract come before an opportunistic core or internal fixation.
Denosumab is not renal-risk free
It avoids bisphosphonate accumulation but severe kidney dysfunction magnifies hypocalcaemia, making biochemical prevention and monitoring more important.
11Common pitfallsFrequent interpretation and management errors.
- 01
Calling progressive night bone pain degenerative without assessing known cancer and focal tenderness.
- 02
Reassuring from a normal radiograph when marrow disease or early cortical involvement remains likely.
- 03
Ordering a bone scan as the universal best test for lytic, myeloma or cord disease.
- 04
Biopsying or fixing a solitary destructive lesion before considering primary bone sarcoma.
- 05
Giving radiotherapy alone to an imminently failing femur.
- 06
Waiting for bladder retention before activating the MSCC pathway.
- 07
Choosing palliative-radiation fractionation without separating uncomplicated pain from fracture or neural compression.
- 08
Starting antiresorptive treatment without calcium, renal and preventive dental assessment.
- 09
Assuming denosumab requires no monitoring because it is not renally cleared.
- 10
Measuring tumour response while neglecting gait, falls, pain, cognition and caregiver burden.