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Paget disease of bone
This condition causes bones to become misshapen, fragile, and prone to fractures, typically affecting individuals over 50 years old. It primarily impacts the pelvis, spine, skull, and long bones of the limbs.
Overview
Paget disease of bone (PDB) is a chronic disorder that disrupts the normal process of bone renewal. In healthy individuals, old bone tissue is continuously broken down and replaced by new bone. In PDB, this process, known as bone remodelling, becomes highly disorganised and accelerated. Cells that break down bone (osteoclasts) and cells that build new bone (osteoblasts) become overactive, leading to new bone that is larger, weaker, and more prone to damage than normal bone [PMID:33675005].
PDB can affect one bone (monostotic) or multiple bones (polyostotic) in the body, although it does not spread from one bone to another. The pelvis, spine, skull, and long bones of the arms and legs are most commonly affected. While the exact prevalence is not precisely known, research suggests it affects 1-3% of individuals over 55 years old in the UK, making it one of the more common bone disorders in older adults.
Symptoms & clinical features
Many people with PDB do not experience noticeable symptoms, and the condition may only be discovered incidentally during X-rays or blood tests for other reasons. When symptoms do occur, they often develop gradually. Common symptoms include bone pain, which can be persistent and severe, and bone deformities. For example, bones in the legs might bow, or the skull might enlarge, leading to changes in hat size.
Other symptoms can arise depending on which bones are affected. If PDB affects the spine, nerve compression can occur, leading to symptoms like numbness, tingling, weakness, or even paralysis in severe cases. Headaches and hearing loss can result from skull involvement. Joint pain, often described as arthritic, may occur in joints adjacent to affected bones, such as the hip or knee.
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Affected organs
PDB primarily affects the skeletal system. Any bone can potentially be involved, but certain bones are more commonly impacted. These include the pelvis, the lumbar (lower back) and thoracic (upper back) spine, the skull, and the femur (thigh bone) and tibia (shin bone) in the legs. These bones may become thickened, enlarged, and develop an abnormal texture. Bone marrow, the soft tissue within bones, can also be affected by the increased bone turnover.
Risks & severity
The severity of PDB can vary significantly among individuals, ranging from asymptomatic to severe and debilitating. The condition typically progresses slowly over many years. One of the main risks associated with PDB is an increased susceptibility to fractures, as the affected bone is weaker and more brittle. These fractures can occur with minimal trauma.
Other potential complications include nerve compression, especially in the spine or skull, which can lead to neurological issues. In rare cases, PDB can lead to high-output cardiac failure due to increased blood flow to affected bones, or the development of a type of bone cancer called osteosarcoma, though this is very uncommon [PMID:36814217]. The condition rarely manifests before the age of 40 and its prevalence increases with age.
Genetic causes
Paget disease of bone is often considered a complex condition, meaning it is influenced by a combination of genetic and environmental factors. Genetic factors play a significant role, with approximately 15-40% of individuals with PDB having a family history of the condition. Pathogenic variants in the *SQSTM1* gene are the most commonly identified genetic cause, accounting for about 10-15% of all PDB cases and a higher proportion (up to 50%) in familial forms [PMID:33675005].
The *SQSTM1* gene provides instructions for making a protein called sequestosome 1, also known as p62. This protein is involved in several cellular processes, including cell signalling and the body's immune response. It plays a crucial role in regulating osteoclast activity - the cells responsible for breaking down bone. Pathogenic variants in *SQSTM1* are thought to lead to hyperactive osteoclasts, disrupting the normal bone remodelling cycle and contributing to the abnormal bone formation seen in PDB.
- SQSTM1 sequestosome 1
Inheritance pattern
Paget disease of bone with *SQSTM1* variants is typically inherited in an autosomal dominant pattern. This means that only one altered copy of the *SQSTM1* gene in each cell is sufficient to increase a person's risk of developing the condition. A person with an autosomal dominant condition has a 50% chance of passing on the altered gene to each of their children, regardless of the child's sex.
It is important to remember that while inheriting an *SQSTM1* variant increases the risk, not everyone with the variant will develop PDB, or they may develop a milder form. This is known as incomplete penetrance, suggesting that other genetic or environmental factors may also influence whether symptoms appear and how severe they are.
Each child has a 50% chance of inheriting the pathogenic variant, regardless of sex.
Diagnosis & testing
Diagnosis of PDB typically involves a combination of clinical assessment, blood tests, and imaging studies. Blood tests often show elevated levels of alkaline phosphatase (ALP), an enzyme related to bone formation, which can be an indicator of active PDB. Genetic testing for variants in the *SQSTM1* gene may be offered, especially for individuals with a strong family history or early-onset disease.
X-rays are crucial for confirming the diagnosis and identifying affected bones, showing characteristic features like bone enlargement, thickening, and abnormal structure. A bone scan (radionuclide bone scintigraphy) can also be used to identify all bones affected by the disease throughout the body. In the UK, genetic testing for PDB falls under the NHS Genomic Medicine Service (GMS) and may be requested by a specialist clinician, with R-code R360 available for targeted testing in specific circumstances.
Management & lifestyle
While there is no cure for PDB, management focuses on controlling symptoms, preventing complications, and normalising bone remodelling. Treatment often involves medications called bisphosphonates, which help to slow down the accelerated bone breakdown and promote the formation of more normal bone. These can be given orally or intravenously.
Pain relief is an important aspect of management, which may include over-the-counter analgesics or prescribed medications. In some cases, orthopaedic surgery may be considered to correct bone deformities, stabilise fractures, or replace damaged joints. Regular monitoring with blood tests (e.g., ALP levels) and imaging studies helps to track disease activity and assess treatment effectiveness. Patients with PDB are typically managed by endocrinologists, rheumatologists, or orthopaedic specialists within the NHS, often with support from genetic counsellors to discuss inheritance risks.
UK care pathway
Within the NHS Genomic Medicine Service, individuals suspected of having a genetic cause for conditions like Paget disease of bone can be referred to a clinical genetics service. This pathway allows for specialist assessment, genetic counselling, and access to genomic testing where appropriate. For Paget disease of bone, targeted gene testing (e.g., for *SQSTM1*) may be available via an NHS R-code, facilitating a precise diagnosis and informing family risk discussions. Genetic counsellors play a key role in explaining complex genetic information and supporting individuals and families through the diagnostic process.
Frequently asked questions
Is Paget disease of bone a type of cancer?
No, Paget disease of bone is not cancer. It is a benign (non-cancerous) condition affecting bone remodelling. While it does rarely increase the risk of a specific bone cancer called osteosarcoma, this complication is very uncommon.
Can Paget disease of bone be passed down in families?
Yes, PDB can run in families, especially if a specific genetic change, such as in the *SQSTM1* gene, is present. It typically follows an autosomal dominant inheritance pattern, meaning each child has a 50% chance of inheriting the genetic variant, though not everyone with the variant will develop symptoms.
What kind of doctor treats Paget disease of bone?
Treatment for PDB is typically managed by specialists such as endocrinologists, who specialise in hormone disorders, or rheumatologists, who specialise in musculoskeletal conditions. Orthopaedic surgeons may also be involved if surgery is needed for fractures or deformities.
What are bisphosphonates and how do they help?
Bisphosphonates are a class of medications commonly used to treat PDB. They work by slowing down the activity of osteoclasts, the cells responsible for breaking down bone. This helps to normalise the bone remodelling process, reduce bone pain, and strengthen the affected bones.
Will I need surgery for Paget disease of bone?
Not everyone with PDB will require surgery. Surgery may be considered in specific situations, such as to repair fractures, correct severe bone deformities, or replace joints that have been damaged due to the condition. Your specialist will discuss if surgery is an appropriate option for you.
References
- Nielsen GP, Jarraya M. Bone Tumor Mimics. Surgical pathology clinics. 2025. PMID: 40716925