[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [General pathology](https://durgical.com/en/general-pathology/) › [Bones, joints and soft tissue](https://durgical.com/en/general-pathology/areas/bone-soft/) › Paget disease of bone

# Paget disease of bone

- Lesion

In Paget disease, overactive osteoclasts and frantic repair make bone that is thick but weak, with a mosaic of cement lines under the microscope.

Updated Nov 13, 2026

## Key points

- Three phases: osteolytic, mixed osteoclastic-osteoblastic, and quiescent osteosclerotic.
- Hallmark histology (sclerotic phase): mosaic pattern of lamellar bone with irregular cement lines (a jigsaw puzzle); the mixed phase lays down woven bone first.
- Isolated, markedly raised alkaline phosphatase with normal calcium and phosphate.
- Complications: fractures (chalk-stick), deformity, hearing loss, nerve compression, high-output heart failure from arteriovenous shunting in bone, and osteosarcoma in a small fraction.
- Giant osteoclasts with up to a hundred nuclei.
- Genes: SQSTM1 (p62) enhances osteoclast signaling.

## What it is

Paget disease of bone (osteitis deformans) is a localized disorder of bone remodelling in older adults. It starts with excessive osteoclast resorption, followed by chaotic new bone formation, and ends in a dense but disorganized bone that is thicker yet mechanically weaker. It affects one bone or several, most often the pelvis, spine, skull, femur and tibia. Mutations of SQSTM1, which encodes a protein in the RANK–NF-κB pathway, explain many familial cases; an environmental trigger, possibly viral, has long been proposed but is unproven.

## Structure

- Lytic phase: huge osteoclasts with very many nuclei and big resorption pits.
- Mixed phase: osteoclasts and prominent osteoblasts side by side, laying down disorganized woven bone; marrow replaced by loose, highly vascular connective tissue.
- Sclerotic phase: thick, coarse trabeculae and cortex with the mosaic of haphazard cement lines; little cellular activity.
- Gross and X-ray: enlarged, thickened bones; skull with patchy 'cotton wool' densities; bowed femur or tibia; flame-shaped lytic front in long bones.

## Step by step

- Osteoclast precursors become hyperresponsive to RANKL and vitamin D (in part through SQSTM1 mutations).
- Giant osteoclasts resorb bone in a localized area at high speed.
- Osteoblasts respond with rapid, disorganized formation of woven and lamellar bone.
- Repeated cycles leave irregular cement lines in a mosaic pattern.
- The result is bigger, denser and more vascular bone that bends, fractures and compresses nerves.

## Clinical notes

- Often found by chance on X-ray or from a high alkaline phosphatase; when symptomatic, causes deep bone pain and warmth over the bone.
- Increasing hat size, deafness from skull involvement, and spinal or cranial nerve compression.
- New pain, swelling or a lytic lesion in a pagetic bone suggests sarcoma (usually osteosarcoma) and needs urgent imaging.
- Bisphosphonates suppress the osteoclast overactivity.

## In the lab

- Alkaline phosphatase is high (bone formation); calcium and phosphate are normal unless the patient is immobilized.
- Bone scan shows the extent of involvement.

## Memory aid

Paget bone is a quilt sewn in a hurry: many patches, crooked seams, warm, thick and easy to tear.

## Test yourself

Think of the answer, then tap the question to see it.

## What is the classic histologic pattern of Paget disease?

A mosaic of lamellar bone pieces separated by irregular cement lines.

## Which lab test is typically high with normal calcium and phosphate?

Serum alkaline phosphatase.

## Why can Paget disease cause high-output heart failure?

Very vascular pagetic bone acts like arteriovenous shunts and increases cardiac output.

## Which malignant tumour can arise in pagetic bone?

Osteosarcoma (secondary osteosarcoma) in a small percentage of patients.

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## Elsewhere in DurgiPedia

- [Bone remodeling](https://durgical.com/en/physiology/bone-remodeling/)
- [Alkaline phosphatase (ALP) as a lab test](https://durgical.com/en/biochemistry/topics/alkaline-phosphatase-as-a-lab-test/)

## Connections

## Related 3

- [Osteosarcoma](https://durgical.com/en/general-pathology/osteosarcoma/)
- [Metabolic bone disease compared](https://durgical.com/en/general-pathology/metabolic-bone-disease-compared/)
- [Fractures and fracture healing](https://durgical.com/en/general-pathology/fractures-and-fracture-healing/)

## Related conditions 2

- [Paget disease of bone](https://durgical.com/en/conditions/paget-disease-of-bone/)
- [Osteosarcoma](https://durgical.com/en/conditions/osteosarcoma/)

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Educational content on the mechanisms of disease; not a diagnostic or treatment guide and no substitute for a health professional's advice. No doses are given.

Sources: [Paget disease of bone: MedlinePlus Genetics](https://medlineplus.gov/genetics/condition/paget-disease-of-bone/) (MedlinePlus, US National Library of Medicine, 2025); [Paget's Disease of Bone | MedlinePlus](https://medlineplus.gov/pagetsdiseaseofbone.html) (MedlinePlus, US National Library of Medicine, 2025).

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Representative model, for educational purposes only.

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Source: https://durgical.com/en/general-pathology/paget-disease-of-bone/
License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/general-pathology/paget-disease-of-bone/