Paget’s Disease of Bone

Aim and objectives

Aim
 To increase knowledge regarding Paget’s disease of bone

Objectives
 To understand the disease process
 To discover what is known about its etiology
 To know the clinical features
 To understand assessment and diagnosis
 To establish the treatment options
 To discover the support available
 Paget’s Disease

A condition where the normal cycle of bone renewal and

repair is disrupted (bone remodelling).

It is characterised by rapid bone remodelling and the

formation of bone that is structurally abnormal.
 Paget’s Disease

 Occurs in 1 – 2 % of white adults over the age of 50 yrs

 Uncommon under the age of 50
 More common in men
 UK has the greatest prevalence of PDB in the world
 The prevalence and severity of the disease has reduced
 Occurs more commonly with advancing age. In the UK, it
presents in approx 8% of men & 5% of women, by the age
of 80.
 Paget’s Disease

How is bone affected?

Normal Bone Remodelling
Abnormalities in Paget’s Disease

Osteoclasts increase in number and size

Increased bone resorption

Increased osteoblast activity to form new bone

New bone is weaker, larger and

abnormal in shape and structure
 Paget’s Disease

Which bones are affected?

 Which bones are affected by PDB?

 Any bone can be affected

 May be monostotic (30-35%) affecting only a single bone

 May be polyostotic (65-70%) involving 2 or more bones

 The disease can progress within an affected bone

 It is uncommon for new sites to appear after initial diagnosis

Bones Commonly Affected
28% Skull

13% Collar Bone

23%
Sternum
4% Upper Arm
7%
Ribs
30% Spine

22% Pelvis

30% Femur

8%
Tibia
Paget’s Disease Under the Microscope

Normal Bone

Woven Bone in Paget’s

Disease
 Paget’s Disease

What are the clinical features

& potential complications?
 Paget’s Disease

• Many people are asymptomatic

• Some have mild to moderate symptoms

• Some have severe symptoms and complications

Clinical features which may be present

 Pain is the most common symptom and is often

unrelieved by rest
 Warmth at the affected site
 Fracture - often following minor injury
 Hearing problems when the skull is involved
 Deformity
- Misshapen, enlarged bone
- bowing of long bones
- enlargement of the head
 Paget’s Disease and Pain

• Bone pain: caused by disease activity

- often described as Persistent and nagging”
- pain at rest, often at night

• Joint pain related to osteoarthritis

• Muscle pain: caused by deformity

• Nerve compression: caused by enlarged bone

• Malignant change: very rare

 Analgesia

• Regular Paracetamol (8 daily)

• Combination therapies (e.g. Co-codamol)

• NSAIDs
Ibuprofen (oral, gel)
Diclofenac
Cox-2 selective inhibitors

• Amitryptylline, Gabepentin
 Potential Complications

Fracture
(fissure or complete) Deafness Deformity
 Potential Complications

Osteoarthritis
Those with PDB are more prone to develop osteoarthritis at
joints adjacent to Pagetic bone

Heart Disease
PDB does not directly affect the heart but in widespread
disease, the heart may have to work harder to pump extra
blood to involved bones.
 Paget’s disease

Assessment &
diagnosis
 Assessment

 Assessment should include

- Full history

- Family history (PDB has a strong genetic predisposition)

- Mobility and functional capacity

- Social history

- Pain
 Investigations

Blood test
A rise in Alkaline Phosphatase (ALP) can
indicate active Paget’s disease

X- ray
Paget’s may be found by chance when an x-ray
is carried out for another reason
Isotope bone scan
This will show the extent and activity of the
disease.

This scan shows evidence of polyostotic disease

(Paget’s in more than one bone)
 Paget’s disease

What causes Paget's disease?

 What causes Paget’s disease?

We are still learning......

There is a general understanding that the disease is due to a
combination of inherited and environmental influences

 It is thought that genetic factors account for about 86% of

the risk of developing Paget’s disease
- mutations have been identified in several genes with
the most important being Sequestosome 1 (SQSTM1)

 Research is inconclusive but exposure to certain viruses

such as measles and other environmental factors may
also influence the development of Paget’s disease
Paget’s Disease

Treatment
 When to treat

• Pain due to active disease

• Consider treatment prior to surgery on an affected bone

• To prevent future problems that might occur if left untreated

 Treatment

• Bisphosphonates (oral or intravenous) reduce the

abnormal bone turnover helping to restore normal
structure and reduce pain.
 Treatment

BISPHOSPHONATES

INTRAVENOUS ORAL

ZOLEDRONATE PAMIDRONATE RISEDRONATE

 Bisphosphonates in Paget’s Disease

 Deposited in the bone

 Reduce abnormal bone turnover
 Reduce pain caused by active disease
 Clinicians find that oral bisphosphonates can return ALP
to normal within 6 months and intravenous within 3
months
 Benefits can last for several months or years

Zoledronate - shown to sustain remission up to 6.5 yrs

 When would surgery be considered?

• Joint replacement

• Fracture repair

• Osteotomy to correct deformity

Bone healing can take longer when

Paget’s Disease is present
 Paget’s Disease?

How did Paget’s Disease get its name?

Sir James Paget

*British surgeon and pathologist

1814 – 1899

*Paget’s disease of bone (PDB)

was named after him

*His name was also given to

Paget’s disease of the nipple &
extramammary Paget’s disease
(these have no other connection
to PDB)
 Sir James Paget

• Sir James Paget described osteitis deformans* in

1876, suspecting a basic inflammatory process

“Holding, then, the disease to be an inflammation of

bones, I would suggest that, for brief reference, and for the
present, it may be called, after its most striking character,
Osteitis deformans. A better name may be given when
more is known of it.”
Medical Chirurgical Transactions, 1877, (60) 37–64.9.
- a medical journal published from 1809 to 1907
*Now referred to as Paget’s Disease
Pictures from the First Publication of
Osteitis Deformans (Paget’s Disease)
 Paget’s Disease

Who can provide support?

 In 1973, the late
Mrs Ann Stansfield MBE
founded the National
Association for the Relief of
Paget’s Disease –
now known as
The Paget’s Association
Aims of the
Paget’s Association
• To inform and support people with Paget’s disease,
their families and carers

• Raise awareness about the condition amongst the

medical profession and the general public

• Encourage, promote and assist research into the

diagnosis, treatment and prevention of Paget’s disease
www.paget.org.uk
Helpline: 0161 799 4646

PowerPoint slides courtesy of the Paget’s Association Feb 2013

References

 Detheridge, F.M., Guyer, P.B., Barker, D.J., (1982) European distribution of Paget’s
disease of bone. BMJ (clinical research edition) 285: 1005 – 8.
 Deyrup, A.T., et al., (2007) Sarcomas arising in Paget disease of bone: a
clinicopathologic analysis of 70 cases. Arch Pathol Lab Med, 131 (6): 942-6.
 Gennari, L., et al. (2010), SQSTM1 gene analysis and gene-environment interaction
in Paget's disease of bone. J Bone Miner Res, 25: 1375–1384.
 Goode, A., Layfield, R., (2010) Recent advances in understanding the molecular
basis of Paget disease of bone J Clin Pathol;63:199e203.
 Langston, A.L., Campbell, M.K., Fraser, W.D., MacLennan, G., Selby, P., Ralston,
S.H. for the PRISM Trial Group, (2007). Clinical determinants of life in Paget’s
disease of bone. Calcif. Tissue Int. 80, 1–9.
 Monsell, E.M., (2004) The mechanism of hearing loss in Paget’s disease of bone.
Laryngoscope 114(4): 598–606
 Paget, J., (1877) A form of chronic inflammation of bones (osteitis deformans).
Medico-Chirurgical Transactions (London) 60: 37-64.
 Poor, G., et al. (2006) Epidemiology of Paget’s Disease in Europe: the prevalence is
decreasing. Journal of Bone and Mineral Research 21: 1545 – 49.
References

 Ralston, S.H., Langston, A.L., Reid, I.R., (2008) Pathogenesis and management of
Paget’s Disease. Lancet 372: 155-63.
 Reid I.R., et al. (2005) Comparison of a single infusion of zoledronic acid with
risedronate for Paget’s disease. New England Journal of Medicine. 353:898-908.
 Reid, I. R., et al (2012) A Single Infusion of Zoledronic Acid Produces Sustained
Remissions in Paget Disease: Data to 6.5 Years. Journal of Bone and Mineral
Research. Sep; 26(9):2261-70.
 Reid, I.R., Hosking, D.J., (2011) Bisphosphonates in Paget's disease. Bone 49, 89–
94
 Sutcliffe, A., (2010) Paget’s: The neglected bone disease. International Journal of
Orthopaedic and Trauma Nursing 14, 142–149
 Van Staa, T.P., Selby, P., Leufkens, H.G., et al. (2002) Incidence and natural history
of Paget’s disease of bone in England and Wales. Journal of Bone and Mineral
Research 17: 465-71.
 Visconti, M. R., et al (2010) Mutations of SQSTM1 are associated with severity and
clinical outcome in paget disease of bone. J Bone Miner Res, 25: 2368–2373