paget's%20bone%20disease
PAGET'S BONE DISEASE
Paget's bone disease, also known as osteitis deformans, is characterized by a significant increase in bone resorption and turnover in localized parts of the skeleton causing enlargement and thickening of the bone that is disordered and architecturally unstable.
The prevalence increases with age, with men and women affected equally.
Genetic factors and/or viral infection may play a role in the etiology.
May affect one bone (monostotic) or several bones (polyostotic).
By decreasing frequency, involved bones may include pelvic bone and sacrum, spine, skull and femur, tibia, humeri and clavicles.

Principles of Therapy

  • Goals of treatment are to ease pagetic pain, reduce activity of the disease, obtain full remission & prevent complications
  • Important to note the location of the pagetic bone lesion & presence of comorbidities in treating asymptomatic patients
    • May initiate treatment if the serum ALP level is >2-4x the upper limit of normal (ULN) value
  • Patients should receive adequate doses of Ca (1500 mg/day) & Vit D (800 units/day) to avoid hypocalcemia
  • Patient should receive pharmacotherapy prior to elective surgery on pagetic site
  • Response to therapy is guided by the following factors:
    • Pain reduction
    • Decrease in serum ALP level & normalization of other bone turnover markers
    • Abnormal bone replacement w/ normal lamellar bone
    • Radiographic imaging
    • Improvement in patient’s quality of life

Pharmacotherapy

Antiresorptive Therapy

Bisphosphonates

  • Eg Alendronic acid, Etidronic acid, Pamidronic acid, Risedronic acid, Tiludronate, Zoledronic acid
  • Inhibit osteoclast activity & decrease bone resorption
  • Decrease bone pain, improve neurological complications, stabilize hearing loss, heal bone lesions
    • Biochemical effects: Decrease by 50% of serum ALP concentrations & urinary excretion of hydroxyproline, pyridinoline & collagen-derived N-telopeptides
    • Prolonged effectiveness; effects remain after years of withdrawal
    • Relatively safe w/ variable side effect profiles among different bisphosphonates
  • Recommended for active Paget’s bone disease patients at risk of future complications & prior to surgery of pagetic bone
  • Bisphosphonates may be used in patients presenting w/ fracture secondary to pagetic bone lesion
    • May be administered once the patient is stable
  • Zoledronic acid is the most potent bisphosphonate approved in the US for Paget’s bone disease
    • Biochemical remissions are sustained & can last up to 1-2 yr in most patients
    • Preferred drug because of its efficacy esp in patients w/ more extensive disease & those who are already on several drug treatment for other conditions
  • Risedronic acid is more effective than Etidronic acid
    • Preferred in younger patients w/ limited disease
  • Alendronic acid is more effective than Pamidronic acid in patients previously treated w/ other bisphosphonates
    • Alendronic acid is also more effective than Etidronic acid
    • Also preferred in younger patients w/ limited disease
  • Associated w/ possible risk of atypical subtrochanteric & diaphyseal femur fractures

Calcitonin

  • 32 amino acid hormone secreted by C cells of the thyroid gland
  • Inhibit osteoclast activity & decrease bone resorption
  • Alternative for patients who cannot tolerate bisphosphonates
  • Decrease bone pain, improves neurological complications, stabilizes hearing loss, heals bone lesions
    • Biochemical effect: Up to 30-50% decrease in serum ALP & urinary hydroxyproline w/in 3-6 mth & remain at these levels as long as treatment continues
    • Short-lived effectiveness; recurrences occur rapidly after withdrawal; high incidence of adverse effects (nausea, flushing)

Pain Management

  • Resorptive therapy generally relieves pagetic pain
  • Manage pain due to bone deformity, arthritis or neurological complications
  • Relieve pagetic pain in addition to resorptive therapy

Paracetamol (Acetaminophen)

  • Analgesic w/ antipyretic properties

NSAIDs

  • Act as non-selective inhibition of cyclooxygenase (COX)-1 & COX-2 pathway
  • Have analgesic, anti-inflammatory & antipyretic properties

COX-2 Inhibitors

  • Selective inhibition of COX-2 pathway w/o inhibiting COX-1 pathway
  • Have analgesic, anti-inflammatory & antipyretic properties w/ reported improved GI tolerance

Non-Pharmacological Therapy

Physical Therapy

  • Improves muscle strength to help control certain types of pain
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