Orthopaedic Surgery - Paget Disease

Basics

Paget disease of bone, also called osteitis deformans, is a chronic disorder of abnormally accelerated and disorganized bone remodeling.

It was first described by Sir James Paget in 1877.

The affected bone may become:

Enlarged

Deformed

Hypervascular

Mechanically weak despite increased density

Any bone may be affected.

Disease can be:

Monostotic, involving a single bone

or

Polyostotic, involving multiple bones.

The distribution is often asymmetric.

Phases of Disease

Paget disease progresses through characteristic remodeling phases.

Early Lytic Phase

The earliest phase is dominated by:

Excessive osteoclastic bone resorption.

Radiographs may show advancing areas of osteolysis.

Mixed Phase

During the mixed phase, there is simultaneous:

Accelerated bone resorption

and

Disorganized new bone formation.

This produces characteristic enlargement and architectural distortion.

Late Sclerotic Phase

Later disease becomes predominantly:

Osteoblastic and sclerotic.

The bone may appear dense but remains structurally abnormal.

Inactive Disease

Some older patients develop metabolically inactive disease with:

No progressive radiographic change

Few or no symptoms

Normal or near-normal biochemical markers

Epidemiology

Paget disease primarily affects:

Middle-aged and older adults.

It is rare before approximately:

40 years of age.

Prevalence rises substantially with increasing age.

Historical Prevalence

Older studies reported disease in approximately:

3–4% of adults older than 50 years

in populations where Paget disease was common.

Prevalence has historically been highest in:

People of European ancestry, particularly in the United Kingdom.

The disease is slightly more common in:

Men.

Geographic Distribution

Paget disease has traditionally been more common in:

Britain

Western Europe

Australia

New Zealand

and populations descended from these regions.

Its prevalence appears to have declined in several countries over recent decades.

Risk Factors

Important risk factors include:

Advancing age

Positive family history

A first-degree relative with Paget disease substantially increases risk.

Genetics

There is strong evidence of a genetic contribution.

First-degree relatives of affected patients have historically been reported to have a risk up to:

Several times greater than that of the general population.

Variants involving genes that regulate:

Osteoclast differentiation and signaling

have been identified in familial disease.

Etiology

The exact cause is not fully established.

Current understanding supports an important:

Genetic predisposition

with possible environmental contributions.

Historical Viral Hypothesis

A slow viral infection involving paramyxoviruses was historically proposed because of:

Long disease latency

Absence of systemic fever

Characteristic osteoclast abnormalities

However, an infectious cause has not been conclusively proven and is not considered an established explanation for most cases.

Pathophysiology

Paget disease begins with excessive:

Osteoclast-mediated bone resorption.

This is followed by a compensatory increase in:

Osteoblast activity and bone formation.

The resulting bone is produced rapidly and lacks the normal organized lamellar architecture.

Abnormal Bone

Pagetic bone may therefore become:

Enlarged

Hypervascular

Sclerotic

yet

Mechanically weaker than normal bone.

This explains the increased risk of:

Deformity

Fracture

Secondary arthritis

Diagnosis

Diagnosis is based on:

Clinical findings

Serum biochemical markers

Plain radiographs

and often

Bone scintigraphy.

Signs and Symptoms

Many patients are:

Asymptomatic.

The disease may be discovered incidentally through:

Elevated alkaline phosphatase

or

Abnormal radiographs.

Bone Pain

When symptomatic, the most common complaint is:

Bone pain.

Pagetic bone pain is often:

Deep

Aching

Persistent

and may be unrelated to activity.

Acute Increase in Pain

A sudden increase in pain should raise concern for:

Pathologic fracture

or, much less commonly,

Malignant transformation.

Skull Involvement

Skull disease may produce:

Frontal bossing

Increase in head size

Headache

Hearing loss

Hearing Loss

Conductive or sensorineural hearing impairment may develop because of:

Temporal bone involvement and alteration of the auditory apparatus.

Spine Involvement

Paget disease of the spine may cause:

Spinal stenosis

Radiculopathy

Neurogenic symptoms

due to vertebral enlargement and narrowing of the spinal canal or neural foramina.

Secondary Arthritis

Pagetic deformity may alter joint mechanics and produce secondary osteoarthritis.

The:

Hip

and

Knee

are particularly commonly affected.

Patients may develop:

Severe joint pain

Stiffness

Reduced walking tolerance

Physical Examination

Local Warmth

Affected superficial bone may feel:

Unusually warm

because of increased vascularity.

This is particularly noticeable in bones such as the:

Tibia.

Deformity

Long-standing disease may produce:

Bowing of long bones

Enlargement of the skull

Angular deformity

Joint Examination

Secondary arthritis may cause:

Restricted range of motion

Pain with motion

Crepitus

Gait disturbance

Hip involvement may significantly restrict:

Internal rotation and flexion.

Neurologic Examination

When the spine or skull is affected, assess for:

Weakness

Sensory change

Radicular symptoms

Gait abnormality

Hearing impairment

Laboratory Tests

Alkaline Phosphatase

The most useful routine biochemical marker is:

Serum alkaline phosphatase.

It is usually elevated when disease is metabolically active.

The level broadly reflects:

The extent and activity of abnormal bone remodeling.

Bone-Specific Alkaline Phosphatase

When total alkaline phosphatase is difficult to interpret because of liver disease, bone-specific markers may be useful.

Bone Resorption Markers

Markers of collagen breakdown may be elevated, including:

N-telopeptide

Hydroxyproline

Pyridinoline cross-links

These are used less commonly than alkaline phosphatase in routine clinical practice.

Serum Calcium

Serum calcium is usually:

Normal.

Hypercalcemia should prompt consideration of another or additional process, such as:

Prolonged immobilization

Hyperparathyroidism

Malignancy

Imaging

Plain Radiographs

Radiographs demonstrate characteristic abnormalities.

Findings may include:

Bone enlargement

Cortical thickening

Coarse trabeculation

Areas of osteolysis

Areas of sclerosis

Bone deformity

Flame-Shaped Lytic Lesion

A classic advancing osteolytic lesion may produce:

A flame-shaped or blade-of-grass radiolucent front, particularly in a long bone.

This is highly suggestive of Paget disease.

Skull Findings

Skull radiographs may demonstrate:

Patchy sclerosis

and the classic:

Cotton-wool appearance

in later stages.

The skull may also become enlarged and thickened.

Pelvic Findings

Pelvic involvement may produce:

Cortical and trabecular thickening

Pelvic brim sclerosis

Protrusio or secondary hip arthritis

Vertebral Findings

Pagetic vertebrae may become:

Enlarged

Sclerotic

with cortical thickening.

This can produce a characteristic:

Picture-frame vertebral appearance.

Bone Scintigraphy

Technetium bone scintigraphy demonstrates:

Increased radionuclide uptake in active lesions.

It is particularly useful for determining:

The full skeletal distribution of disease.

Role of Bone Scan

A bone scan helps determine whether disease is:

Monostotic

or

Polyostotic.

Areas identified on bone scan are often correlated with radiographs.

CT and MRI

CT or MRI may be used when evaluating:

Neurologic compression

Complex deformity

Possible malignant transformation

Atypical lesions

They are not required routinely in uncomplicated disease.

Pathological Findings

Pagetic bone demonstrates:

Very high remodeling activity

with numerous:

Osteoclasts

and

Osteoblasts.

Mosaic Pattern

Repeated cycles of resorption and deposition create numerous irregular:

Cement lines.

This produces the classic histologic:

Mosaic or jigsaw pattern of lamellar bone.

Vascularity

Affected bone is often:

Markedly hypervascular.

This can contribute to increased blood loss during surgery.

Structural Weakness

Although pagetic bone may be dense, it is mechanically disorganized and susceptible to:

Bowing

Microfracture

Pathologic fracture

Differential Diagnosis

Important alternatives include:

Metastatic bone disease

Fibrous dysplasia

Primary bone sarcoma

Paget-associated sarcoma

Metastatic Disease

Metastatic lesions may produce:

Mixed lytic and sclerotic changes

that resemble Paget disease.

Distribution, laboratory findings, imaging morphology, and clinical history help distinguish them.

Fibrous Dysplasia

Fibrous dysplasia may resemble Paget disease radiographically but generally occurs at a:

Younger age

and has different structural characteristics.

Paget-Associated Sarcoma

Malignant transformation should be suspected when a patient with longstanding Paget disease develops:

Rapidly increasing pain

A growing mass

New cortical destruction

A soft-tissue mass

Treatment

General Principles

Not every patient requires treatment.

Therapy is generally directed toward patients with:

Active symptomatic disease

High risk of complications

or

Disease in a location where progression may cause significant morbidity.

Indications for Treatment

Common reasons to treat include:

Pagetic bone pain

Neurologic compression related to active disease

Preparation for surgery involving pagetic bone

Selected lesions at high risk of fracture or deformity

Secondary Arthritis

Pain from secondary osteoarthritis may be treated using:

NSAIDs

Activity modification

Assistive devices

and standard osteoarthritis management.

Assistive Devices

A:

Cane

or

Walker

may help improve:

Balance

Gait stability

Pain control

Physical Therapy

Physical therapy may be used to improve:

Mobility

Strength

Balance

Postoperative rehabilitation

Exercise should be adapted to avoid excessive stress across severely deformed or weakened bone.

Medication

Bisphosphonates

Bisphosphonates are the principal medical treatment for active Paget disease.

They reduce:

Osteoclast-mediated bone resorption

and suppress excessive remodeling.

Mechanism

Bisphosphonates bind to:

Hydroxyapatite in bone

and are taken up by active osteoclasts, reducing their function and survival.

Common Agents

Modern treatment often uses potent agents such as:

Zoledronic acid

because a single intravenous dose can produce prolonged biochemical remission in many patients.

Other bisphosphonates may also be used.

Response to Therapy

Effective treatment generally causes:

Reduction in bone pain

and

Normalization or substantial reduction of alkaline phosphatase.

Bisphosphonate Adverse Effects

Potential effects vary by drug and may include:

Transient flu-like symptoms after intravenous treatment

Gastrointestinal irritation with oral drugs

Hypocalcemia

Renal function and vitamin D status should be considered before therapy.

Calcitonin

Calcitonin inhibits osteoclast function and was historically used frequently.

It may still be considered in selected patients who cannot receive bisphosphonates, but it is generally:

Less effective and less durable.

Potential adverse effects include:

Nausea

Flushing

Preoperative Medical Treatment

When major surgery is planned through highly active pagetic bone, treatment with antiresorptive medication may be considered beforehand to:

Reduce metabolic activity and potentially decrease intraoperative bleeding.

Surgery

The major orthopaedic indications for surgery are:

Joint replacement for secondary arthritis

Fixation of pathologic fractures

Correction of severe deformity

Joint Replacement

Total hip or knee arthroplasty can provide:

Excellent pain relief

and

Substantial functional improvement

in patients with advanced Paget-associated arthritis.

Fracture Fixation

Long-bone fractures often require stable fixation.

For diaphyseal fractures, an:

Intramedullary nail

is often advantageous because it spans a long segment of abnormal bone.

Deformity Correction

Severe long-bone bowing may require:

Corrective osteotomy.

Multiple osteotomies may occasionally be necessary to restore acceptable mechanical alignment.

Surgical Challenges

Operations involving pagetic bone may be complicated by:

Hypervascularity

Excessive bleeding

Bone deformity

Altered anatomy

Poor mechanical quality

Careful planning is therefore essential.

Follow-Up

Patients are followed according to:

Symptoms

Disease activity

Anatomic site

Treatment status

Laboratory Monitoring

Serum alkaline phosphatase is useful for following:

Response to therapy

and

Recurrence of metabolic activity.

Imaging Follow-Up

Plain radiographs are obtained when clinically indicated to monitor:

Deformity

Fracture

Arthritis

Possible malignant transformation

Routine annual radiographs of every involved site are not always necessary in stable asymptomatic disease.

Prognosis

Most patients with Paget disease are:

Asymptomatic or only mildly symptomatic

and have a near-normal life expectancy.

Complications depend primarily on:

The location and extent of affected bone.

Paget-Associated Sarcoma

Malignant transformation is rare, generally occurring in:

Less than 1% of patients.

When it occurs, the tumor is usually a high-grade sarcoma and carries a:

Poor prognosis.

Complications

Pathologic Fracture

Weakened pagetic bone is susceptible to:

Insufficiency and pathologic fractures.

These frequently occur through deformed weight-bearing bones.

Secondary Osteoarthritis

Abnormal alignment may increase loading across nearby joints and lead to:

Progressive degenerative arthritis.

Hearing Loss

Skull involvement may result in progressive:

Hearing impairment.

Neurologic Compression

Vertebral enlargement may cause:

Spinal stenosis

Radiculopathy

and occasionally

Spinal cord compression.

High-Output Cardiac Failure

Extensive active skeletal disease creates increased bone vascularity.

Very rarely, widespread disease can contribute to:

High-output cardiac failure.

Malignant Transformation

Warning features include:

New severe pain

Rapid enlargement

Cortical destruction

Soft-tissue mass

These should prompt advanced imaging and oncologic evaluation.

Patient Monitoring

Patients are commonly reassessed periodically, often:

Yearly in clinically active or significant disease.

Monitoring may include:

Symptoms

Serum alkaline phosphatase

Functional status

Targeted radiographs

Key Principle

Paget disease is a chronic disorder of excessively rapid and disorganized bone remodeling that produces enlarged, hypervascular, and mechanically weak bone.

Most patients do not require treatment, but active symptomatic disease is usually managed with:

Bisphosphonate therapy, while surgery is reserved for complications such as:

Advanced arthritis, pathologic fracture, severe deformity, neurologic compression, or suspected malignant transformation.