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How does Paget disease of bone disrupt the normal balance between bone breakdown and bone formation?
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bone disease
Defect of tibia, caused by septic osteomyelitis in childhood, with compensatory thickening of the fibula (right). Normal bones are shown at left.
Paget disease of bone disrupts the normal balance of bone remodeling by causing both excessive and disorganized bone turnover. In healthy individuals, bone resorption by osteoclasts and bone formation by osteoblasts are tightly coupled and balanced to maintain skeletal integrity.12
In Paget disease, this process becomes chaotic:
- Excessive Resorption: Osteoclasts become extraordinarily active, rapidly dissolving and absorbing bone tissue.1
- Disorganized Formation: These overactive osteoclasts trigger a coupling factor that stimulates local osteoblasts to produce new bone at an excessive and disorganized rate.1
This cycle results in a structurally compromised skeleton. During the bone-destructive phase, bones may soften and become prone to deformity, while the subsequent bone-constructive phase creates dense, brittle bone that is highly susceptible to fracture. This localized or multifocal overgrowth can also lead to pain, arthritis, and, in severe cases, impingement on nerves or the spinal cord.1