Paget disease of bone

01OverviewDefinition, clinical context and the essential points that orientate the chapter.

Paget disease begins with excessive osteoclastic resorption followed by rapid, poorly organised osteoblastic formation. The resulting mosaic bone may be expanded, hypervascular and deformed but structurally weak. Many people are asymptomatic; others report focal deep bone pain, increasing hat size, bowed limb, warmth over superficial affected bone or complications from altered mechanics. Secondary osteoarthritis can dominate pain around a pagetic pelvis or long bone, while vertebral enlargement may narrow the canal. Skull disease can affect hearing through several mechanisms, and bisphosphonate suppression does not reliably reverse established hearing loss. Family history and older age raise probability, but diagnosis depends on characteristic imaging and biochemical context rather than age alone.

The UK Paget guideline recommends total ALP with liver function tests for biochemical screening and radionuclide bone scintigraphy plus targeted radiographs to map metabolically active disease. If total ALP is normal in suspected limited disease, bone-specific ALP or another turnover marker can support specialist assessment. Treatment is indicated primarily for Paget-attributable bone pain; zoledronic acid generally provides the most durable biochemical remission and favourable pain response. Evidence does not support treating every asymptomatic raised marker to prevent future complications, so shared decisions consider site, symptom, planned surgery and risk. Mechanical osteoarthritis may need joint replacement, fracture needs orthopaedic treatment, and neurological compression may require decompression rather than another bisphosphonate. Follow symptoms and ALP after therapy, but investigate recurrent pain even when ALP stays normal because degeneration, fracture or sarcoma can be biochemically silent.

Key points

Paget disease is focal acceleration and disorganisation of bone remodelling, producing enlarged but mechanically abnormal bone in one or several sites.
It becomes more common with age and often affects pelvis, spine, skull, femur or tibia; many patients are detected through raised alkaline phosphatase or incidental imaging.
Use total alkaline phosphatase with liver tests as first-line biochemical screening, then targeted radiographs and a radionuclide bone scan to define active extent.
Paget-related bone pain is usually localised, persistent and sometimes worse at night, but coexisting osteoarthritis, spinal disease and fracture are common alternative pain generators.
Bisphosphonates are recommended for bone pain attributable to active Paget disease, with intravenous zoledronic acid most likely to provide a favourable and durable pain response.
Treat symptoms and complications rather than pursuing normal alkaline phosphatase as an isolated target; intensive biochemical suppression has not improved clinical outcomes.
Hearing loss, skull enlargement, deformity, secondary osteoarthritis, nerve compression and pathological fracture require organ-specific assessment beyond biochemical treatment.
Before bisphosphonate therapy, correct hypocalcaemia and important vitamin D deficiency, assess renal function and obtain dental or jaw-risk review where indicated.

02AetiologyUnderlying causes, associations and risk factors, with why each one matters.

Focal osteoclast dysregulation

Abnormally active osteoclasts initiate excessive resorption in one or more skeletal sites, with the precise initiating cause often not clinically identifiable.

Age and familial susceptibility

Older age and family history increase probability, supporting inherited and acquired influences on focal bone-remodelling control.

03PathophysiologyThe causal sequence from the underlying abnormality to symptoms and harm.

1
Bone resorption accelerates
Overactive osteoclasts remove existing lamellar bone rapidly within affected skeletal regions as the process continues locally.
2
Formation responds excessively
Osteoblasts replace lost tissue quickly but lay down disorganised woven and lamellar bone in a mosaic pattern.
3
Bone enlarges but weakens
The pagetic segment becomes expanded, hypervascular and mechanically abnormal despite increased bulk, causing deformity and altered load transmission.
4
Adjacent structures are affected
Enlarged skull, vertebra or long bone can impair hearing, narrow neural spaces or accelerate secondary osteoarthritis.

04Clinical features and red flagsSymptoms, examination findings, patterns of presentation and time-critical warnings.

Pagetic bone pain

Persistent local aching arising from an affected bone, sometimes with warmth or deformity and without movement dependence, is the principal evidence-based treatment indication.

Incidental active disease

Isolated raised ALP with normal liver markers or characteristic enlargement and cortical thickening on imaging may reveal asymptomatic disease requiring extent assessment rather than automatic therapy.

Mechanical complication

Hip or knee pain linked to movement, restricted range and joint-space loss may reflect secondary osteoarthritis adjacent to pagetic bone and respond poorly to metabolic suppression alone.

Skull or neural disease

Increasing hat size, hearing change, cranial neuropathy, radicular pain, spinal stenosis or cord symptoms indicate anatomical complications needing audiology, neurology or surgical input.

Possible malignant transformation

New relentless focal pain, swelling, mass, fracture or destructive lytic change in previously affected bone is rare but requires urgent sarcoma evaluation.

05InvestigationsWhat to request, why it matters and how to interpret it.

Investigation order

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
Total alkaline phosphatase with liver testsFirst step
Why
Screen for increased bone turnover while distinguishing a likely hepatic source.
Interpretation and limitations
Raised ALP with otherwise non-cholestatic liver tests supports active skeletal turnover but is not specific. Normal ALP does not exclude monostotic or metabolically quiet Paget disease.
02
Targeted plain radiographs
Why
Demonstrate the structural features at symptomatic or suspicious sites and identify deformity, arthritis or fracture.
Interpretation and limitations
Mixed lytic-sclerotic change, cortical thickening, bone expansion and coarse trabeculae support the diagnosis; destructive or aggressive change needs malignancy review.
03
Radionuclide bone scan
Why
Define the distribution and metabolic extent of Paget disease after diagnosis is suspected.
Interpretation and limitations
Increased uptake maps active sites more sensitively than symptoms, but radiographs characterise each important lesion and metastases remain a differential.
04
Bone-specific turnover marker
Why
Assess activity when total ALP is normal despite suspected limited disease or liver disease confounds interpretation.
Interpretation and limitations
Elevation can support active remodelling and follow response, but treatment remains symptom-directed rather than marker-targeted.
05
Calcium, phosphate, vitamin D and renal function
Why
Identify mineral deficits and renal constraints before potent bisphosphonate treatment.
Interpretation and limitations
Correct hypocalcaemia and clinically important deficiency before infusion; reduced kidney function may contraindicate zoledronate or require an alternative specialist strategy.
06
Cause-directed neurological, audiological or cross-sectional imaging
Why
Define nerve, canal, joint or malignant complications that biochemical tests cannot measure.
Interpretation and limitations
Cord compression, severe stenosis, pathological fracture or suspicious mass changes management towards urgent procedural or oncological care.

06Differential diagnosisRealistic alternatives and the features that help distinguish them.

Bone metastasis

Focal pain, abnormal imaging and raised alkaline phosphatase can overlap; characteristic pagetic architecture and cancer evaluation distinguish metastatic destruction.

Fibrous dysplasia

Developmental fibro-osseous lesions often present earlier and show different radiographic distribution and matrix from the mosaic expansion of Paget disease.

Osteoarthritis

Joint-centred mechanical pain may be secondary to pagetic deformity or unrelated; imaging localises degeneration versus active pagetic bone.

Osteomalacia

Diffuse pain, proximal weakness and mineralisation biochemistry suggest systemic osteomalacia rather than focal expanded high-turnover bone.

07ManagementImmediate care, first-line treatment, alternatives and escalation.

01ConfirmDiagnose and map diseaseFirst stepRaised bone ALP, focal bone pain, deformity or an incidental radiograph suggests Paget disease.

1Separate bone from liver ALP, take a focused skeletal and neurological history and obtain targeted radiographs of suspicious sites.
2Use radionuclide bone scanning to map active distribution and image clinically important scan-positive sites when characterisation remains incomplete.
3Review calcium-vitamin D, renal function, pain source and complications with a metabolic bone specialist before deciding whether treatment will improve symptoms.

02TreatTarget Paget-related bone painPain is attributable to metabolically active pagetic bone and treatment is not contraindicated.

1AlternativeCorrect mineral deficiency, assess kidneys and dental risk, explain acute-phase effects and agree whether intravenous zoledronic acid or an alternative best fits the person.
2Administer the licensed specialist regimen and provide symptom-directed analgesia and rehabilitation rather than relying on biochemical suppression alone.
3Review pain and ALP after the expected response interval; if pain persists with biochemical suppression, investigate osteoarthritis, fracture or another cause.

03ComplicationEscalate structural diseaseEscalationDeformity, arthritis, hearing loss, neural compression, fracture or suspicious focal progression dominates the presentation.

1Obtain anatomical and functional assessment appropriate to the site, including urgent neurological imaging when cord, cauda equina or cranial nerve function is threatened.
2Refer joint degeneration or fracture to an experienced orthopaedic service, planning bleeding and deformity considerations around surgery.
3Send a rapidly progressive destructive lesion through a sarcoma pathway and avoid assuming that another bisphosphonate course addresses malignant or mechanical pathology.

Key medicines and prescribing safety3 treatments · regimens, roles and cautions

Potently suppresses excessive osteoclast activity and is the bisphosphonate most likely to produce a durable biochemical and favourable bone-pain response.

Zoledronic acid for Paget disease

Give the licensed single intravenous Paget regimen through a specialist service after confirming hydration, calcium-vitamin D sufficiency and renal eligibility; repeat treatment is based on relapse and symptoms rather than scheduled annual infusion.

Acute-phase reaction, hypocalcaemia and kidney injury occur. Check creatinine clearance, avoid in severe renal impairment, review dental and jaw risk, and distinguish this regimen from osteoporosis or oncology schedules.

Provides an oral antiresorptive option that reduces disease activity and can improve Paget-related pain.

Risedronate for Paget disease

Use the licensed daily oral Paget course for the defined treatment duration when intravenous zoledronate is unsuitable, following strict fasting and upright administration instructions.

Avoid in significant oesophageal disease, inability to remain upright, hypocalcaemia or renal function below the product limit. Adherence to daily administration determines absorption, and response may be less durable than zoledronate.

Treats osteoarthritis, deformity-related or residual pain that does not reflect active pagetic remodelling.

Analgesia for mechanical or residual pain

Select paracetamol, a topical option or another locally recommended analgesic according to age, kidney, gastrointestinal and cardiovascular risk, and review ongoing need rather than escalating automatically.

NSAIDs can worsen renal and gastrointestinal risk, while opioids increase falls and dependence. Analgesic response does not establish the source, and new focal pain needs structural reassessment.

08ComplicationsImportant consequences, why they occur and why they matter clinically.

Deformity and fracture

Disorganised enlarged bone bows under load and remains structurally weak, increasing painful deformity and pathological fracture risk.

Secondary osteoarthritis

Altered shape and load transmission across nearby joints accelerates cartilage degeneration and can dominate the person's pain and disability.

Hearing loss

Skull involvement can alter cochlear, neural and conductive structures, causing hearing impairment that may not reverse when turnover is suppressed.

Neurological compression

Vertebral or skull expansion can narrow neural canals and cause radiculopathy, spinal compromise or cranial-nerve dysfunction.

09Monitoring and follow-upTreatment response, safety checks and longer-term review.

Review Paget-attributable pain and function after bisphosphonate treatment; symptom improvement is more meaningful than biochemical normalisation alone.
Measure ALP or the selected turnover marker after the expected response interval and later when symptoms recur, using the same marker for comparability.
Monitor calcium and renal function after potent therapy in people with high turnover, deficiency, frailty or kidney risk.
Ask about hearing, neurological function, deformity, falls and joint limitation at follow-up because structural complications may progress independently of ALP.
Escalate new swelling, rapidly worsening focal pain or fracture promptly even if the last turnover marker was normal.

10Special situationsVariants, exceptions and circumstances that change the usual approach.

ALP reflects burden

Extensive active polyostotic disease often raises total ALP, while a small monostotic lesion may not. Marker normality is partly a question of skeletal volume.

Pain source determines response

Bisphosphonate can improve active pagetic bone pain but will not reliably reverse advanced adjacent osteoarthritis or spinal stenosis. Localise the pain before retreating.

Treat-to-target failed clinically

Trials found no advantage from intensive ALP normalisation over symptom-led therapy for preventing complications. Biochemical neatness is not the therapeutic goal.

Bone scan maps, radiograph names

Scintigraphy is sensitive for distribution; plain imaging shows the characteristic architecture and important structural complications. They answer complementary questions.

Hearing loss is heterogeneous

Skull involvement, ossicular mechanics and neural factors can contribute. Suppressing turnover does not guarantee hearing recovery, so audiological management remains necessary.

Relapse pain needs a new diagnosis

After durable zoledronate response, recurrent pain with normal ALP may be degenerative, fractured or rarely malignant rather than biochemical Paget relapse.

11Common pitfallsFrequent interpretation and management errors.

01
Diagnosing Paget disease from raised ALP without liver tests and characteristic skeletal imaging.
02
Treating an asymptomatic biochemical marker repeatedly merely to keep ALP normal.
03
Assuming all hip pain beside pagetic pelvis is active bone pain rather than secondary osteoarthritis.
04
Giving zoledronic acid before correcting hypocalcaemia, vitamin D deficiency or assessing renal function.
05
Using an osteoporosis zoledronate schedule automatically for Paget disease without checking the licensed indication.
06
Reassuring new destructive focal pain because sarcomatous transformation is rare.