A 2014 clinical practice guideline from the Endocrine Society defined Paget’s disease of bone (osteitis deformans) as a chronic, benign disorder that affects one or more bones. It begins with bone resorption by large osteoclasts followed by a high rate of formation of poorly organized bone, resulting in both a marked increase of bone cell activity and abnormal bone structure.122
The authors of the 2014 Paget’s Disease of Bone Endocrine Society Clinical Practice Guideline estimated that rates of Paget’s disease in the US are approximately 2-3% among patients ≥ 55 years and suggested a 10-20% incidence of autosomal dominant transmission within families affected by the disease.122
The sequestosome 1 gene, which affects osteoclast biology, has been implicated in familial Paget’s disease,123,124 and various studies have reported that mutations in this gene occur in 25-50% of patients with familial Paget’s disease.125 Other studies have concluded that genetic mutations alone are insufficient to cause the disease, and that exposure to environmental factors (e.g., measles virus nucleocapsids or other factors) are likely involved.126 Still other researchers have highlighted an increased prevalence of vitamin D deficiency in Paget’s disease patients.127 Because most patients are asymptomatic, disease discovery typically is empirical and results from either elevated serum alkaline phosphatase levels or a radiograph or bone scan ordered for another disorder. The most frequently affected bones are the pelvis, vertebrae, skull, femur, and tibia.122
A retrospective case review in Hong Kong from 2000 to 2010 identified seven patients (5 men, 2 women, mean age 66) with x-ray or CT findings of Paget’s disease.128 Most patients had polyostotic disease, and during follow-up did not present any Paget’s disease-related complications or malignant transformations. Investigators studying pharmacologic treatments reported similar results (see next section).
According to the Endocrine Society guideline, pharmacological treatment of both asymptomatic and symptomatic patients involves bisphosphonates.122 A recent review generally concurred with these findings, but noted that treatment benefits in asymptomatic patients are controversial and are not evidence-based and thus should be individualized with careful monitoring.129 This author summarized studies that compared the efficacy of different bisphosphonates in the treatment of Paget’s disease and concluded that zoledronic acid is an attractive option, in part because it does not have the negative gastrointestinal effects associated with oral bisphosphonates that often lead to noncompliance. Others have reported similarly favorable outcomes following treatment with zoledronic acid.130-132 Denosumab, a monoclonal antibody that binds to RANKL and inhibits osteoclastic bone resorption, has been used in some patients who do not respond well to bisphosphonates. Calcitonin, which was used before bisphosphonates became widely available, shows untoward side effects and generally should be used only in patients who cannot tolerate bisphosphonates.129
Several studies have suggested that the occurrence and severity of Paget’s disease is declining worldwide. Other studies have reported the effectiveness of pharmaceutical agents in reducing pain, improving patients’ quality of life, normalizing bone turnover, and healing lytic lesions.125 Conditions associated with Paget’s disease are generally of greater clinical concern than the disease itself. For example, Pagetic osteosarcoma is a rare complication of Paget’s disease. A group of Italian researchers found that between 1961 and 2006, patients treated at their hospital for Pagetic osteosarcoma had poor outcomes following surgery either with or without subsequent chemotherapy or radiotherapy.133