Paget Disease of Bone Overview

Overview of Paget Disease of Bone

• Paget disease of bone involves excessive bone remodeling in certain areas.
• Bone resorption is followed by excessive bone growth.
• This leads to skeletal deformities and potential fractures.
• Also known as osteitis deformans.
• The bones become thick, weak, and deformed.
• Commonly affects the pelvis, femur, and lower lumbar spine, but can affect any bone.
• Associated with an increased risk of fractures, arthritis, and bone tumors.
• Symptoms include bone pain, arthritis, and nerve impingement.

Bone Remodeling Process

• Normally, bones undergo continuous remodeling.
• Old bone is reabsorbed by osteoclasts, which are multinucleated bone cells with 5-20 nuclei.
• Resorbed bone is replaced by new bone made by osteoblasts.
• Osteoblasts release RANKL, which binds to RANK receptors on osteoclasts, activating them.
• Activated osteoclasts secrete lysosomal enzymes like collagenase and hydrochloric acid.
• These enzymes digest collagen and dissolve minerals in the bone matrix.
• Osteoblasts then secrete osteoprotegerin (OPG), which binds to RANKL, preventing osteoclast activation and halting demineralization.
• Osteoblasts secrete osteoid seam, mainly made of collagen, which acts as a scaffold for calcium and phosphate deposition, forming new bone.

Causes of Paget Disease

• The exact cause is unclear.
• Infections like measles and genetic mutations, such as the SQSTM1 mutation, are linked to the disease.
• The SQSTM1 mutation affects a protein that regulates osteoclasts.

Affected Bones

• Paget disease can affect a single bone or the entire skeletal system.
• Commonly involves the skull, lumbar vertebrae, pelvis, and femur.

Phases of Paget Disease

• Lytic phase: Osteoclasts with up to 100 nuclei aggressively demineralize bone at up to 20 times the normal rate.
• Mixed phase: Lytic and blastic phases occur simultaneously.
• Blastic phase: Rapid, disorganized proliferation of new bone tissue by many osteoblasts, resulting in haphazard collagen fiber deposition.
• Sclerotic phase: New bone formation exceeds bone resorption, resulting in structurally disorganized and weaker bone.

Treatment

• Medications, such as bisphosphonates, slow disease progression.
• Pain relievers manage symptoms.
• Surgery corrects deformities or stabilizes fractures.