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SatuVehkavaara

Paget's Disease of Bone (Osteitis Deformans)

Paget's disease is a chronic metabolic disorder of unknown aetiology that affects the skeleton. It is characterised by rapid local bone resorption followed by chaotic new bone deposition, which leads to abnormally structured bone at one or several sites in the skeleton.
Lesions are most typically found in the skull, spine, pelvis and long bones of the lower extremities.
The disease is asymptomatic in the majority of patients, but it can cause local symptoms that include pain, fractures, nerve entrapments and bone tumours. Plasma alkaline phosphatase concentration is increased.
Often found incidentally on imaging studies.

Unknown aetiology
Affects the middle-aged and elderly populations; symptoms that would lead to diagnosis are usually not observed in patients less than 50 years of age.
There is also a juvenile form of the disorder causing a severe progressive bone disease.
Slightly more common in men than in women
The disease is most common in England, Scotland, Central Europe and Greece, and least common in Scandinavia and Finland (less than 1 per thousand) and Asia.
In studies conducted in the US and England, 12-13% of the patients have been found to have a relative with the disease. Hence, genetic factors have a role in the pathogenesis of the disease.
The prevalence is steadily decreasing. The severity of the disease is decreasing and the number of people with symptomatic disease is decreasing.
The disease is associated with a risk of osteosarcoma (found in less than 1% of patients).

The majority of patients are asymptomatic, often diagnosed incidentally when investigating the cause of increased plasma alkaline phosphatase concentration or interpreting bone x-rays.
The most common symptom is pain at the site of the lesion. It is usually continuous in nature and bothers also in rest and during the night.
May manifest as pathological fractures and predispose to osteoarthritis of adjacent joints.
The lesions may in the cranial bones and spine cause severe nerve entrapment: loss of hearing, spinal stenosis and symptoms resembling radiculopathy.
Severe forms are becoming rarer.

The first radiological finding is a local osteolytic lesion, which, if not treated, will grow slowly (less than 1 cm in a year). As the disease progresses, both lytic and sclerotic changes are typical. In an advanced disease sclerotic changes are predominant. Thickening of the bone cortex also often occurs (picture 1).
A bone scan will show the extent of the disease. The most common is a single area of increased uptake.
Plasma alkaline phosphatase (ALP) is usually increased at the active phase of the disease. When investigating an indeterminate increase in ALP, an ALP isoenzyme assay will detect increased activity of the skeletal isoform in the disease. Plasma calcium concentration is normal.
It may sometimes be difficult to differentiate the disease from malignancies (e.g. prostate or breast cancer metastases, lymphoma) especially in spinal lesions.
- Findings in the spine may be confirmed by a CT scan or MRI.
In some cases, a bone biopsy may be indicated.

In symptomatic patients, treatment is always indicated.
Asymptomatic patients are treated if ALP is significantly increased in line with disease activity or if imaging findings are associated with a significant risk of complications (e.g. vertebral or cranial).
Bisphosphonates inhibit osteoclast activity and also affect the structure of the newly formed bone. Currently, the preferred option is a single infusion of zoledronic acid. In one study, ALP normalised with a single infusion in 96% of patients 4.
The majority of patients maintain treatment response for 5-6 years, a small proportion for up to 10 years. The treatment can be repeated, as necessary.
Diagnosis and treatment of the disease are usually the responsibility of specialized care. During the follow-up, attention is paid to the emergence of symptoms and the level of plasma alkaline phosphatase.

Ralston SH, Corral-Gudino L, Cooper C et al. Diagnosis and Management of Paget's Disease of Bone in Adults: A Clinical Guideline. J Bone Miner Res 2019;34(4):579-604. [PubMed]
Al-Rashid M, Ramkumar DB, Raskin K ym. Paget Disease of Bone. Orthop Clin North Am 2015;46(4):577-85. [PubMed]
Singer FR. Paget's disease of bone-genetic and environmental factors. Nat Rev Endocrinol 2015;11(11):662-71. [PubMed]
Reid IR, Miller P, Lyles K et al. Comparison of a single infusion of zoledronic acid with risedronate for Paget's disease. N Engl J Med 2005 Sep 1;353(9):898-908. [PubMed]
Cundy T, Maslowski K, Grey A et al. Durability of Response to Zoledronate Treatment and Competing Mortality in Paget's Disease of Bone. J Bone Miner Res 2017;32(4):753-756. [PubMed]