Biology and Treatment of Paget's Disease of Bone

Abstract

Paget's disease of bone (PDB) is a common skeletal disorder characterized by increased and disorganized bone remodeling affecting one or more skeletal sites. Although some patients are asymptomatic others develop complications such as bone pain, deformity, nerve compression syndromes, and fragility fractures. Genetic factors play an important role in the pathogenesis of PDB and there is strong evidence that susceptibility is determined by variants within or close to genes that regulate osteoclast function. Environmental factors also play a key role but the nature of the environmental triggers is less clear. Bisphosphonates are a highly effective treatment for the elevations in bone turnover that are characteristic of PDB but it is unclear at present if they alter the natural history of the disease. Here, we review the epidemiology, clinical, cellular, and molecular abnormalities in PDB as well as environmental and genetic triggers, and current available treatment options.

Sphingosine 1-phosphate signaling in bone remodeling: multifaceted roles and therapeutic potential

“…Osteoporosis, by way of example, is characterized by low bone mass and decreased bone strength; patients with osteoporosis are at high risk of fragility fractures of the vertebrae or hip. In contrast, bone diseases such as Paget’s disease or osteopetrosis are characterized by high bone mass, while, remarkably, bone strength is also decreased [14–17]. …”

PSMA-PET/CT-Positive Paget Disease in a Patient with Newly Diagnosed Prostate Cancer: Imaging and Bone Biopsy Findings

“…Paget disease is a common disorder of the skeleton characterized by hypertrophic and abnormally structured remodeling of bone [9, 10]. Many patients are asymptomatic, whereas others suffer from pain, nerve compression, or even pathologic factures.…”

“…Many patients are asymptomatic, whereas others suffer from pain, nerve compression, or even pathologic factures. Rarely, malignant degeneration (osteosarcoma) may occur [9, 10]. Genetic and environmental factors play a role in the pathogenesis [10].…”

“…Rarely, malignant degeneration (osteosarcoma) may occur [9, 10]. Genetic and environmental factors play a role in the pathogenesis [10]. Bisphosphonates are used for treatment; it is, however, unknown whether they influence the national history of the disease [10].…”

Headache in patients with Paget’s Disease of Bones

“…Patients with skull involvement tend to show less biochemical response to treatment 22 . In clinical practice, paracetamol and nonsteroidal antiinflammatory drugs (NSAIDs) are used as symptomatic treatment for mild or intermittent pain 38 . A clinical trial with a large cohort of 1324 PDB patients compared intensive bisphosphonate treatment to symptomatic treatment with analgesics or NSAIDS followed by bisphosphonates for non-responders, with a mean time of follow up of 3 years 39 .…”