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

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 30% Femur 28% Skull 13% Collar Bone 23% Sternum 7% Ribs 4% Upper Arm 30% Spine 22% Pelvis 8% Tibia

Normal Bone Paget’s Disease Under the Microscope 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

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 Paget’s Disease and Pain

Regular Paracetamol (8 daily) Combination therapies (e.g. Co-codamol) NSAIDs Ibuprofen (oral, gel) Diclofenac Cox-2 selective inhibitors Amitryptylline, Gabepentin Analgesia

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

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) Blood test A rise in Alkaline Phosphatase (ALP) can indicate active Paget’s disease Investigations X- ray Paget’s may be found by chance when an x-ray is carried out for another reason

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

Pain due to active disease Consider treatment prior to surgery on an affected bone To prevent future problems that might occur if left untreated When to treat

Treatment Bisphosphonates (oral or intravenous) reduce the abnormal bone turnover helping to restore normal structure and reduce pain.

BISPHOSPHONATES INTRAVENOUS ZOLEDRONATE PAMIDRONATEORALRISEDRONATE Treatment

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?

* 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)

“ 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– a medical journal published from 1809 to 1907 Sir James Paget described osteitis deformans* in 1876, suspecting a basic inflammatory process *Now referred to as 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 Helpline: 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): 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: 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: 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: 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): 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: 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