Updated: 3/17/2018

Paget Disease of Bone

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Snapshot
  • A 65-year-old man presents with worsening left-sided hearing loss and mild headache. He reported that his symptoms began a few months prior to presentation. He denies starting any new medications but has noticed he can no longer fit the hat he has owned for many years. Physical examination is unremarkable. Laboratory testing is notable for an elevated serum alkaline phosphatase. A radiograph of the skull is shown. 
Introduction
  • Clinical definition
    • a progressive metabolic bone disorder of abnormal bone remodeling 
      • there is excessive bone resorption and formation resulting in
        • immature woven bone with collagen fibers arranged irregularly
  • Background
    • adult bone constantly undergoes bone remodeling and is accomplished by
      • osteoclasts
        • contains receptor activator for NF-κB (RANK) transmembrane receptors which
          • responds to RANK ligand (RANKL) on osteoblasts and osteocytes to differentiate and activate in order to resorb bone
      • osteocytes
        • secrete growth factors to regulate bone formation
          • bone formation is stimulated when mechanical forces are applied to bone
        • contains RANKL
      • osteoblasts
        • contain RANKL and osteoprotegerin (OPG)
          • OPG inhibits RANKL from binding to RANK on osteoclasts, thus inhibiting bone remodeling
        • functions in bone formation
    • bone matrix has two histological forms
      • woven
        • has less structural integrity
        • seen in fetal development and fracture repair
        • always considered abnormal in adults
      • lamellar
        • has more structural integrity
  • Pathogenesis
    • genetic and environmental factors may be involved
    • increased multinucleated osteoclastic and osteoblastic activity leads to a high bone remodeling rate, leading to
      • abnormal bone architecture
    • phases
      • lytic phase
        • intense osteoclastic resorption
      • mixed phase
        • resorption and compensatory bone formation
      • sclerotic phase
        • osteoblastic bone formation predominates
      • all three phases may co-exist in the same bone
  • Associated findings
    • neurologic
      • nerve root compression
      • hearing loss
      • spinal stenosis
    • orthopedic
      • pathologic fractures
      • secondary osteoarthritis
    • oncologic
      • osteosarcoma
    • cardiovascular
      • high-output heart failure
    • labs
      • normal serum phosphate, calcium, and parathyroid hormone 
      • elevated alkaline phosphatase 
    • histology
      • mosaic pattern of lamellar bone with prominent cement lines
Normal Biology and Anatomy
  • adult bone constantly undergoes bone remodeling and is accomplished by
    • osteoclasts
      • contains receptor activator for NF-κB (RANK) transmembrane receptors which
        • responds to RANK ligand (RANKL) on osteoblasts and osteocytes to differentiate and activate in order to resorb bone
    • osteocytes
      • secrete growth factors to regulate bone formation
        • bone formation is stimulated when mechanical forces are applied to bone
      • contains RANKL
    • osteoblasts
      • contain RANKL and osteoprotegerin (OPG)
        • OPG inhibits RANKL from binding to RANK on osteoclasts, thus inhibiting bone remodeling
      • functions in bone formation
  • bone matrix has two histological forms
    • woven
      • has less structural integrity
      • seen in fetal development and fracture repair
      • always considered abnormal in adults
    • lamellar
      • has more structural integrity
Laboratory Abnormalities in Select Bone Disorders
Etiology
Serum Phosphate
Serum Calcium
Serum Alkaline Phosphatase
Parathyroid Hormone
Osteomalacia/rickets 
  • Decreased
  • Decreased
  • Increased
  • Increased
Osteoporosis 
  • Normal
  • Normal
  • Normal
  • Normal
Osteopetrosis
  • Normal
  • Normal or decreased
  • Normal
  • Normal
Paget disease of bone 
  • Normal
  • Normal
  • Elevated
  • Normal
Osteitis fibrosa cystica
  • Primary
    hyperparathyroidism
    • decreased
  • Secondary
    hyperparathyroidism
    • increased
  • Primary
    hyperparathyroidism
    • increased
  • Secondary
    hyperparathyroidism
    • decreased
  • Primary and secondary hyperparathyroidism
    • increased
  • Primary and secondary hyperparathyroidism
    • increased
Hypervitaminosis D
  • Increased
  • Increased
  • Normal
  • Decreased
 
Presentation
  • Symptoms
    • usually asymptomatic
    • bone and/or joint pain
    • bone deformity
      • bowing deformity
    • hearing loss 
      • with skull involvement that lead to narrowing of the auditory foramen
  • Physical exam
    • typically unremarkable
Treatment
  • Medical
    • bisphosphonates
      • mechanism of action
        • impregnates the bone that will be acted upon by osteoclasts
          • when osteoclasts release the bisphosphonates during resorption, it impairs osteoclast activity
 

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(M1.MK.13.7) A 55-year-old male presents with left hip pain and stiffness. Radiographs are shown in Figures A and B. Serum alkaline phosphatase levels are elevated. A biopsy of the left femur is performed and shown in Figure C. Which of the following cells are initially responsible for this condition?

Tested Concept

QID: 101944
FIGURES:
1

Osteoblasts

26%

(6/23)

2

Osteoclasts

61%

(14/23)

3

Neutrophils

0%

(0/23)

4

T-Cells

0%

(0/23)

5

Fibroblasts

9%

(2/23)

M 2 E

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