Description

• Focal disorder of hyperactive bone resorption followed by excessive bone formation (remodeling) that is stimulated by abnormal osteoclasts
• Results in enlarged, disorganized, weakened, and highly vascularized mosaic of bone
• Painful condition, with easily deformed bone that is subject to fractures from minimal trauma
• Most commonly affected sites:
  • Pelvis, spine, skull, extremities
• Cranial and vertebral involvement can lead to neurologic deficits.
• Synonym(s): Paget disease of bone; osteodystrophia deformans

Epidemiology

• Predominant age: >50 years
  • Less common in patients from ages 20 to 50 years
  • Does not occur in children (Juvenile Paget disease is unrelated to the adult disease.)
• Predominant sex: males > females (1.8:1)

Prevalence

• Prevalence increases with increasing age.
  • 2% among 55- to 59-year-old men, 20% among men >85 years (1)[C]
• More common if Caucasian, especially in United Kingdom, France, Germany, Italy, United States, Australia, or New Zealand
  • 3% of Caucasians >50 years have at least one gene focus.
• Rare in African Americans and Asians
• Incidence and prevalence have decreased in recent years; likely due to genetic and environmental factors

Etiology and Pathophysiology

• Unknown, although several theories proposed:
  • Slow viral infection (controversial): due to paramyxovirus, respiratory syncytial virus, canine distemper virus and measles; causing expression to develop over many years
  • Zoonotic infections
  • Toxin occupational exposure
  • Childhood malnutrition—vitamin D deficiency or low dietary calcium
• Three pathologic phases:
  • Lytic phase: Osteoclasts are large, contain 10 to 100 nuclei, and have abnormal configuration.
  • Mixed phase: Excessive osteoblastic bone formation predominates from increase in number of osteoblasts; nonlinear collagen deposition results.
  • Sclerotic phase: Sclerotic bone–containing cement lines form a mosaic pattern (woven bone), with vasculature infiltration and fibrous connective tissue deposition.

Genetics

• At least seven genetic loci have been identified that are associated with Paget disease of bone.
• Mutations in SQSTM1, predominately ubiquitin-binding associated (UBA) domain and P392L, are associated. Product of SQSTM1 affects osteoclast differentiation and activation.

Risk Factors

• First-degree relative with osteitis deformans (OD)
  • 15–30% of patients note a family history of OD.
• Caucasian and European ethnicity

General Prevention

Fracture reduction: Avoid excessive mechanical stress on afflicted bones.

Commonly Associated Conditions

• Hyperparathyroidism
• Gout
• Secondary osteoarthritis
• Peyronie disease
• Accelerated atherosclerosis
• Osteoporosis circumscripta
• Frontotemporal dementia (rare)
• Hereditary inclusion body myopathy (rare)
• Bone sarcoma (rare)