Skip to textbook content
Doctor’s PassportTextbook
TopicsAll topics

Loading topic navigation…

Textbook navigation
TopicsAll topics

Loading topic navigation…
← Endocrinology and metabolism indexChapter sections
OverviewAetiologyPathophysiologyClinical features and red flagsInvestigationsDifferential diagnosisManagementComplicationsMonitoring and follow-upSpecial situationsCommon pitfallsQuestionsSources
Full textbook13 sectionsOpen only what you need
Educational draft · awaiting clinical reviewThe full textbook explains uncertainty but does not replace live national or local guidance, specialist advice, or current prescribing information.

Paget disease of bone

Endocrinology and metabolism · UK scope · Sources checked 27 Aug 2026 · Clinical review pending

RapidFull
!
Neurological compression or pathological fracture changes urgency

New weakness, sensory loss, sphincter disturbance, acute hearing or cranial nerve change, severe focal pain with fracture, or a rapidly enlarging painful bone lesion needs urgent imaging and specialist assessment. Rare sarcomatous transformation should be considered when established Paget disease develops rapidly progressive focal pain, swelling or destructive imaging.

Action: Assess ABCDE and neurovascular status, immobilise a suspected fracture, provide analgesia and obtain urgent targeted imaging. Discuss spinal compression, skull-base compromise, pathological fracture or possible malignancy with orthopaedics, spinal surgery, neurology or sarcoma services rather than waiting for routine alkaline phosphatase review.

Overview

Recognise focal disordered bone remodelling, define its skeletal extent, treat Paget-related pain and distinguish complications requiring surgical or urgent specialist care.

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.

Practice

Two practice questions

Your practice draft is saved in this browser.

Question 1 of 2
0 correct
Endocrinology and metabolismOriginal SBA

Indication for Paget treatment

An older adult has radiographic Paget disease of the pelvis, raised bone alkaline phosphatase and persistent focal pelvic bone pain attributed to active disease. Which treatment principle is best supported?

Choose one answer, then submit
← Rapid synopsisBack to overviewAll Endocrinology and metabolism topics →
Sources and review status4 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.

  • UK Paget disease clinical guidelineDiagnosis, imaging, symptom-directed treatment and key recommendations.
  • Paget Association clinical managementALP, bone scanning, zoledronate and complication management.
  • Paget Association professional resourcesFull endorsed guideline and UK professional implementation materials.
  • Paget Association treatment guidanceUK treatment choices and safety information grounded in the clinical guideline.

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
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.

Aetiology

01

Focal osteoclast dysregulation

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

02

Age and familial susceptibility

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

Pathophysiology

  1. 1
    Bone resorption accelerates

    Overactive osteoclasts remove existing lamellar bone rapidly within affected skeletal regions as the process continues locally.

  2. 2
    Formation responds excessively

    Osteoblasts replace lost tissue quickly but lay down disorganised woven and lamellar bone in a mosaic pattern.

  3. 3
    Bone enlarges but weakens

    The pagetic segment becomes expanded, hypervascular and mechanically abnormal despite increased bulk, causing deformity and altered load transmission.

  4. 4
    Adjacent structures are affected

    Enlarged skull, vertebra or long bone can impair hearing, narrow neural spaces or accelerate secondary osteoarthritis.

Clinical features and red flags

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.

Investigations

  1. 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.
  2. 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.
  3. 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.
  4. 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.

Differential diagnosis

01

Bone metastasis

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

02

Fibrous dysplasia

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

03

Osteoarthritis

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

04

Osteomalacia

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

Management

01ConfirmDiagnose and map diseaseFirst stepRaised bone ALP, focal bone pain, deformity or an incidental radiograph suggests Paget disease.+
  1. 1Separate bone from liver ALP, take a focused skeletal and neurological history and obtain targeted radiographs of suspicious sites.
  2. 2Use radionuclide bone scanning to map active distribution and image clinically important scan-positive sites when characterisation remains incomplete.
  3. 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.+
  1. 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.

Complications

01

Deformity and fracture

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

02

Secondary osteoarthritis

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

03

Hearing loss

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

04

Neurological compression

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

Monitoring and follow-up

  • 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.

Special situations

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.

Common pitfalls

  1. 01

    Diagnosing Paget disease from raised ALP without liver tests and characteristic skeletal imaging.

  2. 02

    Treating an asymptomatic biochemical marker repeatedly merely to keep ALP normal.

  3. 03

    Assuming all hip pain beside pagetic pelvis is active bone pain rather than secondary osteoarthritis.

  4. 04

    Giving zoledronic acid before correcting hypocalcaemia, vitamin D deficiency or assessing renal function.

  5. 05

    Using an osteoporosis zoledronate schedule automatically for Paget disease without checking the licensed indication.

  6. 06

    Reassuring new destructive focal pain because sarcomatous transformation is rare.

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.
  • 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.+
    1. 1Obtain anatomical and functional assessment appropriate to the site, including urgent neurological imaging when cord, cauda equina or cranial nerve function is threatened.
    2. 2Refer joint degeneration or fracture to an experienced orthopaedic service, planning bleeding and deformity considerations around surgery.
    3. 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.