At diagnosis, Paget’s may be symptomatic or clinically silent, present in one bone or many, and its distribution in any given patient (best determined by isotope bone scan) tends to remain constant over time. It is characterised by focal areas of increased bone resorption and formation, resulting in expanded but structurally weak bone, prone to deformity, fracture and (rarely) sarcomatous change.
Prevalence is highest in the UK, followed by Australia, New Zealand and North America.
Archaeological studies suggest it first arose in Roman Britain (1 to 400 AD), and then spread, following patterns of European migration. Radiographic surveys in the 1970s, found the disease affected 5% of those over 55 in England and 3% of Western Australians. Since then, the incidence and severity of new cases have each shown a marked decline. The disease is now becoming a rarity.
Genetic and environmental factors
The aetiology of Paget’s disease is only partly understood; its geographic distribution and frequent occurrence within families suggest genetic predisposition, confirmed in recent studies. An autosomal dominant form of the disease is caused by germline mutations in the SQSTM1 gene, found in about 25% of affected kindreds, and 5-10% of patients with no family history. In the remaining patients with familial and sporadic disease, the disease is polygenic, with common variants in at least 8 genes (identified in genome association studies) predisposing to its development.
The rapid decline in disease incidence and severity (observed even in kindreds with autosomal dominant disease) point to a declining influence of environmental factors but these remain largely speculative. A viral origin for Paget’s disease (long postulated), is supported by in vitro models but conclusive proof is lacking. Other suggested environmental factors (with little evidence) include local trauma to bone, environmental toxins, tobacco smoking and calcium nutrition.
Nowadays, Paget’s disease is most commonly diagnosed incidentally on diagnostic imaging or because of raised alkaline phosphatase activity on liver function testing.
A minority of patients have symptomatic disease, most commonly pain in affected bones or secondary arthropathy. Severe, deforming, polyostotic disease (common 20-30 years ago), is now rarely seen. Treatment is indicated in symptomatic patients and those whose disease distribution puts them at risk of future complications (e.g. involvement of long bones or base of skull).
The treatment of choice is a single dose of intravenous zoledronic acid, which induces long lasting remission of disease in most cases. Oral bisphosphonates can also be used, but high dose treatment for several months is required, making intravenous treatment preferable.
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- Once a very common disease of the elderly, Paget’s disease of bone is now rare (for unclear reasons).
- The disease has a strong genetic basis but the environmental factors involved are largely unknown.
- Bisphosphonate treatment is for symptomatic patients or those at risk of complications from affected sites.
Britton C, Walsh JP. Paget disease of bone: an update. Australian Family Physician 2012; 41: 100-103 https://www.racgp.org.au/afp/2012/march/paget-disease-of-bone/
Paget’s Disease of Bone: An Endocrine Society Clinical Practice Guideline https://doi.org/10.1210/jc.2014-2910
[https://www.healthdirect.gov.au/pagets-disease-of-bone (this is for patients)]
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