The most commonly affected bones are the pelvis, the spine, the femora, and the skull but practically any bone of the skeleton may be affected and there is remarkable similarity in the frequency of affected bones in large series of patients from different countries. About one- third of patients have only one lesion (Figure 1) but the frequency of single lesions varies among series, probably reflecting referral patterns, and is higher in asymptomatic patients. Notably, the anatomical spread of skeletal lesions in Paget’s disease is log normally distributed and the commonly used distinction in clinical practice to monostotic and polyostotic disease is not pathophysiologically appropriate. The anatomical spread of the disease is not related to age or gender, shows no particular symmetry in the body, and remains largely unchanged throughout life. The disease progresses slowly within the affected bone but does not generally appear in other bones. Patients with limited bone involvement should, therefore, be reassured that the disease will not progress to other bones with time.
Fig1. Monostotic Paget’s disease illustrated by bone scintigraphy: (a) right pelvis; (b) right tibia (with deformity and fracture); (c) vertebra.
The majority of patients are asymptomatic and the disease may be diagnosed incidentally during investigation of an unrelated com plaint by skeletal radiographs or by the finding of an unexplained elevation of serum alkaline phosphatase activity. About 5– 10% of affected patients have symptoms. Skeletal morbidity in Paget’s disease is determined by the damage caused and the progression of the disease in affected sites as well as by the number and the localization of the lesions. Extensive disease, as originally described by Sir James Paget, occurs in about 5% of symptomatic patients. This is in agreement with the limited chance of an individual to develop extensive disease, as predicted by the distribution of lesions, but changing patterns of the disease to milder forms may also contribute to that.
The symptoms and complications of Paget’s disease,(summarized in Table 1), can have great impact on the quality of life of affected individuals. In the majority of patients, the presenting complaint is pain. This is related to the extent and site of the disease, it is usually persistent and present at rest, but is not specific. Pain due to secondary osteoarthritis is common and may hamper assessment of the relative contribution of bone and joint pains to the patient’s disability. The origin of such pain can be assessed only retrospectively after treatment which reduces mainly the disease- related pain, having a rather limited effect on the arthritic pain. Deformities are present in about 15% of patients at the time of diagnosis and affect mainly weight- bearing bones, the most common deformity being bowing of the lower limbs. About 9% of patients present with fractures, which can be complete or fissure (incomplete) fractures. The latter occur more frequently, can be multiple, can cause pain, and may develop to complete fractures. Fractures heal generally well although in an older report of 182 fractures of the femur the incidence of non- union was 40%. The skin overlying an affected bone may be warm as a result of increased blood flow and bone turnover locally and hypervascularity of affected bones may cause ischaemia of adjacent structures (steal syndrome). Irreversible hearing loss is the most common neuro logical complication occurring in about one- third of patients with skull involvement. This is thought to be related to structural and/ or density changes in the cochlear capsule bone. Neoplastic transformation of pagetic bone is rare (less than 1%) and includes osteosarcoma and giant cell tumours associated more frequently with familial clustering of the disease. Pathogenic mutations of the ZNF687 gene were identified in a family with Paget’s disease with increased prevalence of giant cell tumours of bone but also in patients with or without SQSTM1 mutations. The ZNF687 gene is highly expressed during osteoclast and osteoblast differentiation and patients with missense mutations of the gene had an earlier clinical expression and more severe bone disease.
Table1. Symptoms and complications of Paget’s disease of bone
