PAGET DISEASE OF THE BONE
- Definition and Pathology
- Also called osteitis deformans.
- Characterized by uncontrolled, highly active, large osteoclasts → increased bone resorption.
- Marked compensatory osteoblastic activity causes new bone that is disorganized (lacking normal lamellar structure).
- Increased local bone blood flow and fibrous tissue in the adjacent marrow.
- Prevalence ~3% in adults >40 years; often asymptomatic, evolves slowly.
- Epidemiology
- Same prevalence in men and women, but more commonly symptomatic in men.
- Typically detected in the sixth decade of life.
- Often found incidentally (e.g., elevated alkaline phosphatase on labs or suspicious findings on radiographs).
CLINICAL MANIFESTATIONS
- Symptoms
- Bone pain due to periosteal stretching or microfractures; worse with weight bearing.
- Warmth over the affected bone from increased local blood flow.
- Can be monostotic (one bone) or polyostotic (multiple).
- Most commonly involves pelvis, spine, femur, skull, tibia.
- Femur/tibia: Bowing of legs, gait changes.
- Spine: Kyphosis, possible spinal cord compression.
- Skull: Hearing loss (cranial nerve VIII compression), skull deformities (frontal/occipital), rare facial nerve palsy.
- Others: Visual disturbances (optic nerve), platybasia, hydrocephalus (skull base involvement).
- Complications
- Fractures (transverse; low threshold because of bone architecture).
- Bony neoplasia: Increased frequency of giant cell tumor, fibrosarcoma, chondrosarcoma, osteosarcoma.
- Primary hyperparathyroidism more frequent.
- High-output cardiac failure when >20% of skeleton is involved (increased vascularity).
EVALUATION
- History & Examination
- Evaluate for bone pain, skeletal deformities, hearing changes, possible nerve compressions.
- Imaging
- Radionuclide bone scan: Focal areas of increased uptake in pagetic bone.
- Plain radiographs: Confirm Paget disease, assess extent (e.g., lytic, mixed, or sclerotic lesions).
- Laboratory
- Serum alkaline phosphatase: Typically elevated in active disease.
- Calcium: Normal unless immobilization or coexisting hyperparathyroidism.
- Additional Tests
- Serum calcium to assess for hyperparathyroidism.
- Audiogram if skull involvement.
- Bone biopsy if suspicion of malignancy or if imaging is inconclusive.
- Markers of Bone Turnover
- Bone formation markers: Bone-specific alkaline phosphatase, osteocalcin, propeptides of type I collagen (PINP).
- Bone resorption markers: Urinary hydroxyproline, collagen crosslinks (N-telopeptide, C-telopeptide).
- In Paget disease, both formation and resorption markers increase and normalize with successful treatment.
PATHOGENESIS AND TREATMENT
- Potential Cause
- Believed to be viral (paramyxovirus) trigger + genetic predisposition.
- Viral inclusions found in pagetic osteoclasts.
- ~30% have family history of Paget disease; SQSTM1 (sequestosome 1) mutations implicated.
- When to Treat
- Many patients asymptomatic → no treatment needed if minimal disease.
- Indications: Pain, risk of bone or nerve complications, moderate-high disease activity, extensive skull involvement, major weight-bearing bones, or younger patients.
- Main Goal
- Suppress osteoclast activity.
- Bisphosphonates
- First-line therapy to inhibit osteoclasts.
- Examples: etidronate, pamidronate, alendronate, tiludronate, risedronate, zoledronic acid.
- Routes: High-dose oral or IV.
- Effective for remission >1 year in many cases.
- Side effects:
- IV forms → ~20% get transient ‘flu-like’ symptoms 1–2 days after infusion.
- Oral forms → esophageal irritation; must take upright, fasting, with water.
- Monitoring: Discontinue once bone turnover markers normalize; retreat if/when they rise again.
- Other Therapies
- Calcitonin: Historically used but less potent than bisphosphonates.
- Plicamycin (mithramycin): Rarely used (toxicity).
- Supportive
- Adequate calcium and vitamin D supplementation.
- Monitor 25-hydroxyvitamin D levels to ensure repletion.
- Physical therapy, analgesics for pain control.