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.
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.
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.
Elsewhere in DurgiPedia
Connections
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 (MedlinePlus, US National Library of Medicine, 2025); Paget's Disease of Bone | MedlinePlus (MedlinePlus, US National Library of Medicine, 2025).
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Representative model, for educational purposes only.