Bone metastases and pathological fracture

• Bone is the third most common site of cancer spread after the lungs and liver, and roughly 70% of metastatic bone disease is seen with prostate, breast or lung cancer. ^[2]
• Most bone metastases are osteolytic (bone-destroying); prostate cancer is the main exception, producing osteoblastic (bone-forming) lesions. ^[1]
• A pathological fracture is a fracture through bone weakened by tumour, often after minimal or no trauma.
• We predict impending fracture with the Mirels score: 4 parameters, each scored 1 to 3; a total of 9 or more calls for prophylactic fixation. ^[3]
• Bone-targeted agents (zoledronic acid 4 mg IV or denosumab 120 mg subcutaneously every 4 weeks) reduce skeletal-related events but do not save a patient who already has an unstable bone. ^[6]
• Spinal metastases are an emergency when neurological signs appear: MRI of the whole spine within 24 hours and dexamethasone 16 mg. ^[4]

By the end of this page you should be able to:

1. Explain which primary cancers spread to bone most often, and whether the resulting lesion is usually lytic or sclerotic.
2. Recognise a pathological or impending fracture clinically and on imaging, and separate it from osteoporosis and primary bone tumours.
3. Calculate a Mirels score and state the fracture risk and management that each band implies.
4. Outline the role of bisphosphonates and denosumab: doses, route, interval, renal caution and monitoring.
5. Plan palliative radiotherapy fractionation for painful bone metastases and for spinal cord compression.
6. Decide when prophylactic internal fixation is needed and which construct is used.
7. Recognise spinal cord compression early, start the correct drug and imaging, and cross-check with the spinal cord compression page.
8. Adapt the whole approach to settings where MRI, radiotherapy or orthopaedic surgery is not available.

This page covers the whole pathway: which cancers spread to bone, how the lesions look, how fracture risk is estimated, drug and radiotherapy treatment of skeletal disease, and when and how to fix a bone surgically. It cross-checks with the spinal-cord-compression-and-myelopathy and multiple-myeloma topics. Guidelines used are the ESMO 2020 bone-health-in-cancer guideline, NICE NG234 (2023, last reviewed 2026) for spinal disease, and the ASCO focused guideline update (2011) for bone-modifying agents, together with the XGEVA labelling (2026).

A related useful distinction is between an actual pathological fracture, where the cortex has broken, and an impending pathological fracture, where a lesion has weakened the bone so much that fracture is judged imminent but has not yet occurred. That judgement is what the Mirels score exists for. ^[3]

Classification by radiological appearance matters more than by primary site for practical decisions:

• Osteolytic (lytic) lesions are darker on X-ray because bone has been destroyed. They carry the higher fracture risk.
• Osteoblastic (sclerotic) lesions are denser and look white on X-ray. They are far less likely to fracture, although the abnormal bone is still weak. ^[1][2]
• Mixed lesions contain both elements and are common in breast cancer.

Bone is the third most common organ affected by metastasis, after the lungs and liver. ^[2] Metastatic bone disease occurs in a large proportion of patients with the common solid tumours:

More detailed primary-specific figures from a recent review are consistent with these ranges: about 75% of patients with advanced breast cancer, more than 70 to 85% of patients with advanced prostate cancer, about 40% of patients with non-small cell lung cancer, about 30% of patients with renal cell carcinoma, and 1 to 20% of patients with differentiated thyroid carcinoma develop bone metastases. ^[1] These cancers together account for roughly 70% of the metastatic bone disease that clinicians see. ^[2]

Once bone is involved, the consequences are frequent. Among patients who present without a skeletal-related event, later skeletal-related events occur in 47% of patients with lung cancer, 46% with prostate cancer and 52% with breast cancer during follow-up. ^[2] Pathological fracture, spinal cord compression and the need for analgesic radiotherapy or surgery are all skeletal-related events and they carry a real penalty in survival: pathologic fractures carry up to a 32% increased risk of death compared with the absence of a pathologic fracture. ^[2]

Spinal involvement is particularly common. Spinal metastases are reported in 30 to 50% of patients with advanced malignancies, and the thoracic spine is involved in about 70%, the lumbar spine in about 20% and the cervical and sacral spine in about 10%. ^[1]

Survival after a bone metastasis depends heavily on the primary tumour: mean survivals after a skeletal complication are thyroid 26 months, breast 19 months, prostate 18 months, and lung 6 months; among surgically treated non-spinal bone metastases the longest median survival is in myeloma (26 months). ^[2]

There is no modifiable lifestyle risk factor for bone metastasis; the risk follows the primary cancer and its biology. Bone metastasis is a staged process: cancer cells leave the primary tumour, travel in the bloodstream, become dormant in bone marrow, and later reactivate and recruit osteoclasts and osteoblasts. ^[1] The bone marrow is a friendly environment for these cells, and different primaries prefer different bone sites. The spine, pelvis, proximal femur and humerus are the common sites, reflecting rich cancellous bone and blood supply. ^[1]

Risk factors that raise fracture risk in a patient who already has a lesion include:

• Lytic appearance and a lesion larger than about two-thirds of the bone diameter. ^[3]
• Lesion in a weight-bearing bone, especially the peritrochanteric proximal femur. ^[3]
• Ongoing or worsening mechanical pain. ^[3]
• Prior radiotherapy to the lesion that failed to control it. ^[4]
• Low bone mineral density from cancer treatment (for example, androgen deprivation therapy or aromatase inhibitors), which compounds the risk.

The virtuous circle of normal bone remodelling is broken. Tumour cells in bone secrete factors that activate osteoclasts; osteolysis in turn releases growth factors stored in bone matrix that feed the tumour. ^[1] In lytic disease (breast, lung, kidney, thyroid) osteoclasts dominate and holes form in cortex and trabeculae. In prostate cancer the dominant picture is osteoblastic, yet the new bone is disorganised and mechanically inferior, so fractures still occur. ^[1]

Because of this, lesion type predicts fracture risk: lytic lesions fracture more often than sclerotic lesions. ^[2] Pain also has a mechanical component: a lesion that hurts when the bone is loaded is signalling reduced strength before the bone actually breaks.

Bone metastasis usually presents with one of three patterns:

• Pain is the commonest symptom. It is often dull, constant, worse at night, and exacerbated by movement or weight bearing.
• Pathological fracture: the patient reports a crack or snap doing something trivial, often followed by severe pain and loss of function.
• Incidental finding on staging or follow-up imaging in a patient with already-known cancer. Some lesions are silent until they fracture.

Red flags in the history:

• Back pain in a patient with known cancer is spinal metastasis until excluded.
• New weakness, numbness, or bladder or bowel dysfunction suggests spinal cord compression and is an emergency.
• Hypercalcaemia of malignancy presents with polyuria, thirst, constipation, confusion or abdominal pain.

Look and feel for:

• Localised tenderness over the affected bone.
• Reduced range of movement if a joint is involved.
• Deformity, bruising or inability to bear weight after a fracture.
• Neurological examination of the limbs and perineum when spinal disease is possible: motor power, sensation including a sensory level, reflexes, and anal tone.
• Signs of the primary cancer if it has not yet been diagnosed: breast lump, prostate enlargement, lymphadenopathy, hepatomegaly.

Investigations answer three questions: where is the primary, how extensive is bone disease, and is fracture imminent.

• Plain X-ray of the symptomatic bone is the first test and should not be skipped: it shows lytic or sclerotic change, cortical breakthrough and fracture.
• Isotope bone scan (technetium-99m) is good at mapping the whole skeleton for metastases, especially for blastic disease; purely lytic lesions can be missed.
• CT of the affected bone gives detail of cortical destruction and helps with surgical planning.
• MRI of the whole spine is the investigation of choice for spinal metastases and for spinal cord compression. ^[4]
• PET-CT is increasingly used for staging, particularly in lung, breast and myeloma, and may replace bone scan in some pathways.
• Blood tests: full blood count, renal function, calcium, phosphate and alkaline phosphatase; serum protein electrophoresis if myeloma is possible; tumour markers where useful.

Red flag imaging findings that push for urgent orthopaedic or neurological referral: cortical breakthrough in a weight-bearing bone, a lesion beyond about half the bone diameter, an avulsion or fracture line, or any epidural extension with cord compression signs. ^[1][3]

The Mirels score is the standard clinical tool for deciding whether an impending fracture of a long bone needs prophylactic fixation. It adds four components, each scored 1, 2 or 3: ^[3]

The interpretation, drawn from Mirels' original work as summarised in a recent review: ^[3]

• 7 or lower: fracture risk about 4%; mostly avoid prophylactic fixation.
• 8: fracture risk about 15%, false-positive rate about 6%. ^[3]
• 9: fracture risk about 33%, no false positives in the original data. ^[3]
• Lesions scoring 9 or more require prophylactic surgical stabilisation. ^[3]
• The original Mirels data were derived from long bones and humeral lesions may behave differently: studies suggest a lower cut-off of 7 for the humerus to retain sensitivity. ^[3]

In practice the score is combined with clinical judgement: persistent pain that is mechanical, imaging that shows cortical breach, and the patient's overall prognosis and mobility. Newer techniques (CT-based structural rigidity analysis, finite element analysis) predict fracture better than Mirels in the proximal femur, but are not universally available. ^[3]

The doses, routes and monitoring below follow the ASCO 2011 focused guideline update for bone-modifying agents, ^[5] the ESMO 2020 bone health guideline ^[7] and NICE NG234 for spinal disease. ^[4]

Suspected spinal cord compression is treated as an emergency. New neurological symptoms in a patient with cancer (weakness, sensory level, gait disturbance, bladder or bowel dysfunction, or bilateral radicular pain) warrant immediate contact with an oncology service. ^[4]

• Start dexamethasone 16 mg by mouth, or an equivalent parenteral dose, as soon as possible, and continue 16 mg daily while awaiting surgery or radiotherapy. ^[4]
• Immobilise if spinal instability is suspected or pain is moderate to severe. ^[4]
• MRI of the whole spine should be obtained as soon as possible and always within 24 hours. ^[4]
• Plain X-ray of the spine is not a substitute and should not be relied on to exclude spinal metastases or spinal cord compression. ^[4]
• Analgesia, including opioids, should not be delayed while investigations are underway. ^[4]
• Radiotherapy for spinal cord compression, where surgery is not appropriate, should be given within 24 hours of the decision to treat. ^[4]
• After radiotherapy or surgery the steroid dose is tapered gradually. ^[4]

Bone-targeted agents are the main drug treatment for bone metastases. They do not cure cancer but reduce skeletal-related events: fractures, radiotherapy courses, surgery and spinal cord compression.

• Zoledronic acid 4 mg intravenously over no less than 15 minutes every 3 to 4 weeks. ^[5] Some health systems use a 15-minute infusion and others a longer one; follow local labelling.
• Pamidronate 90 mg intravenously over no less than 2 hours every 3 to 4 weeks. ^[5]
• Denosumab 120 mg subcutaneously every 4 weeks. ^[5][6]
• One agent is not considered superior to another in head-to-head trials; choose on route, renal function, tolerance and cost. ^[5]

Contraindications and cautions: ^[5][6]

• Correct hypocalcaemia before starting, because all agents can worsen it.
• Give oral calcium and vitamin D supplements during treatment. ^[6]
• In renal impairment: no change in dose or interval is required when calculated creatinine clearance is above 60 mL/min; zoledronic acid has dose adjustments for creatinine clearance 30 to 60 mL/min in its labelling; denosumab has not been evaluated below 30 mL/min or in dialysis, so monitor calcium closely in these patients. ^[5][6]
• Monitor serum creatinine before each intravenous bisphosphonate dose.
• Dental assessment and necessary preventive dentistry before starting, and good oral hygiene throughout, because of osteonecrosis of the jaw.
• Do not combine two bone-targeted agents.

Radiotherapy gives fast and reliable pain relief for focal painful bone metastases.

• For spinal metastases without cord compression, in non-mechanical spinal pain: 8 Gy in a single fraction, even if paralysed, or stereotactic ablative body radiotherapy for patients with good overall prognosis or with up to three discrete metastases anywhere in the body (oligometastases). ^[4]
• For metastatic spinal cord compression not suitable for surgery: 8 Gy in a single fraction unless at high risk of side effects (large field or previous radiotherapy), in which case multiple fractions. ^[4]
• For asymptomatic spinal metastases, routine radiotherapy is not recommended outside a trial; consider it only for oligometastatic disease or radiological signs of impending compression. ^[4]
• A single 8 Gy fraction is usually favoured in palliative practice because one visit suffices and durability is adequate for most patients.

Surgery is used to restore stability and function, control pain, and allow weight bearing. Common constructs:

• Intramedullary nail for diaphyseal (shaft) lesions of the humerus or femur, often cement-augmented.
• Plate and cement for selected distal femoral or proximal (metaphyseal) lesions.
• Endoprosthetic replacement of the proximal femur or humerus for large destructive lesions where fixation is not secure.
• Spinal fixation and decompression (separation surgery plus stabilisation) when there is mechanical instability or neurological compromise and the patient has sufficient life expectancy.

Prophylactic fixation of long-bone lesions before fracture occurs eases pain, allows earlier ambulation and costs less than treating a completed fracture. ^[2]

For vertebral lesions, minimally invasive options include vertebroplasty and kyphoplasty for painful vertebral collapse, with better analgesia than medical treatment alone in selected patients. ^[1]

• Analgesia following standard palliative cancer pain ladders; nerve blocks and image-guided procedures where appropriate. Bone-targeted agents are adjuncts to analgesia, not first-line analgesics. ^[5]
• Immobilisation and bracing for mechanical pain or unstable spine segments.
• Early mobilisation with physiotherapy after fixation.
• Radiotherapy adjunct to control pain.
• Psychological support and rehabilitation.

• Reassess pain and neurological status regularly, escalate if new pain appears.
• Repeat skeletal imaging to judge response; bone scan or CT/MRI depending on the primary cancer.
• Dental monitoring and prompt treatment of any oral symptoms, because of osteonecrosis of the jaw.
• Continue bone-targeted agents until substantial decline in general performance status. ^[5]
• Monitor renal function and calcium, phosphate and magnesium during treatment. ^[5]

• Suspected spinal metastases with pain, and all spinal cord compression: contact the oncology service promptly. ^[4]
• A Mirels score of 9 or more, or an actual pathological fracture: refer to orthopaedic oncology/trauma.
• Pathological fracture in a previously unknown primary: biopsy and work-up before fixation where feasible.
• Severe or difficult pain: refer to specialist pain or palliative care.
• Hypercalcaemia of malignancy: treat urgently with intravenous fluids and, where appropriate, a bone-targeted agent; endocrine/oncology input is needed. ^[6]

• Pathological fracture, sometimes requiring surgery and prolonged rehabilitation.
• Spinal cord compression, with paraparesis or paraplegia if untreated.
• Hypercalcaemia of malignancy, managed with fluids and a bone-targeted agent.
• Intractable pain, sometimes requiring palliative radiotherapy or nerve blocks.
• Skeletal-related events generally, which reduce survival and quality of life. ^[2]
• Treatment effects from bone-targeted agents: hypocalcaemia, hypophosphataemia, osteonecrosis of the jaw, atypical femoral fracture, renal impairment.

Prognosis is governed by the primary tumour and the presence of visceral metastases, not by the bone lesion alone. Mean survival after a skeletal-related event is thyroid cancer 26 months, breast cancer 19 months, prostate cancer 18 months, and lung cancer 6 months; among surgically treated non-spinal metastases the longest median survival is in myeloma (about 26 months). ^[2] A pathological fracture itself worsens survival, with up to a 32% increased risk of death compared with no pathological fracture. ^[2]

For otherwise fit patients with a single metastasis (breast or kidney) and good life expectancy, metastasectomy or aggressive local treatment can add useful time; for the majority, treatment is palliative and aims to prevent events and relieve pain.

There is no screening test for bone metastases. Prevention has two parts:

• Early detection through careful questioning about bone pain and plain X-ray of any symptomatic bone in a cancer patient.
• Prevention of skeletal-related events with bone-targeted agents as above, starting once bone metastases are confirmed. ^[5][7]
• Cancer-treatment-induced bone loss is a separate problem (aromatase inhibitors, androgen deprivation therapy) and is covered in its own topics; it raises baseline fragility and compounds the risk from a metastasis.

• Renal impairment. Use zoledronic acid with caution and dose adjustment between creatinine clearance 30 and 60 mL/min; it is not evaluated below 30 mL/min. Denosumab is not evaluated below 30 mL/min or in dialysis; monitor calcium closely. ^[5][6]
• Dental health. All patients should have a dental examination and preventive dentistry before starting a bone-targeted agent, then maintain oral hygiene and avoid invasive dental procedures. ^[5][6]
• Older adults. Frailty, renal function and life expectancy all affect whether a major fixation is worthwhile; use prognostic scores and discuss goals of care.
• Pregnancy. Bone-targeted agents are contraindicated or require specialist advice; management is by the cancer and obstetric team.
• Children. Bone metastases in childhood are usually part of a high-risk primary (for example Ewing sarcoma or neuroblastoma); see the childhood-bone-tumours topic.

• A plain X-ray of a painful or loaded bone, combined with the cancer history, confirms or excludes most fractures and many lytic lesions.
• A bone scan is cheap and widely available and remains useful for mapping whole-skeleton disease.
• MRI of the spine may be a 24-hour journey away; if neurology is threatened, start dexamethasone 16 mg empirically and arrange transfer. ^[4]
• When radiotherapy is unavailable, the same single-fraction schedule can sometimes be arranged at a regional centre; analgesia and orthopaedic fixation become the main tools.
• Zoledronic acid is much cheaper than denosumab and is stocked in most oncology units; denosumab may be preferred when renal function is poor.
• Prophylactic intramedullary nailing is simple and durable even in small hospitals with basic X-ray control.

• spinal cord compression and myelopathy
• multiple myeloma
• primary bone tumours in adults
• adult orthopaedic injuries
• hypercalcaemia
• lung cancer
• prostate cancer (part 2)
• Paget disease of bone