Paget disease of bone (PDB) is a remarkable disorder of aging bone. It was first described by Sir James Paget in 1877, in his paper entitled “On a Form of Chronic Inflammation of Bones (Osteitis Deformans).” In this sentinel paper, Paget catalogues the progressive deformity of bone that occurs over 26 years in an individual man, detailing the enlargement of his head, the settling of the skull over the spine, the evolving rigidity of the spine and bowing of the lower limbs. “The shape and habitual posture of the patient were thus made strange and peculiar.” Paget attributed these skeletal changes to chronic inflammation of the affected bones, and called the disease osteitis deformans, writing “a better name may be given when more is known of it.”

• Often asymptomatic; however, pain, early arthritis in proximal joints and bone fractures are common complications. Osteosarcomas develop in a small minority of patients.
  
• Accelerated bone remodeling results in enlarged, misshapen bone.
  
• Usually presents in persons older than 55 years.

PDB is a focal disorder of bone remodeling that tends to present in individuals middle-aged or older. PDB is often associated with no other problem other than that due to progressive deformity of bone and is often asymptomatic. Treatment is effective and should be aimed at preventing disease progression as well as treating pain arising from pagetic bone.

Paget disease is a rich area of study, as genetic as well as environmental determinants are sought to explain the skeletal distribution and late onset of this disease. PDB affects males perhaps slightly more than females and exists as a familial disease with variable penetrance. It may also exist as a sporadic disease. It usually presents in persons older than 55, and does not occur in children. PDB is remarkable for the geographic clusters of disease as well.

Paget disease is presumed a disorder of the osteoclast, although it is clear that the bone marrow environment plays a critical role in permitting the accelerated bone turnover that characterizes this disease. In 2002, a consistent mutation in SQSTM1 was identified in almost 50% of a Canadian cohort of patients with familial PDB, as well as in 16% of those with “sporadic disease.” This mutation is often present on a shared haplotype, suggesting a founder effect. However, the predominance of the SQSTM1 mutations present in the Canadian cohort is not found in other countries. How genes might interplay in the environment of aging bone disease or whether viruses or other environmental determinants may prove permissive to this focal disorder of bone is unknown.

Symptoms and Signs

PDB is often asymptomatic, detected incidentally on a radiograph, or diagnosed in the course of evaluating an elevated serum alkaline phosphatase. It may be monostotic (one bone) or polyostotic (many bones). The process of accelerated bone remodeling that defines this disease results in enlarged, misshapen bone that softens and loses skeletal integrity. Pain, early arthritis at proximal joints, and fractures are a few salient symptoms of PDB, with deformity not infrequent in weight-bearing limbs. When PDB affects the skull, the overgrowth may lead to deafness, headache and, rarely, more serious neurologic impairment (such as dementia and apathy) as the bones thicken, vascular “steal” occurs, and basilar invagination develops.