Paget's%20bone%20disease Treatment

• Goals of treatment are to ease pagetic pain, reduce activity of the disease, obtain full remission and prevent complications
• Important to note the location of the pagetic bone lesion and presence of comorbidities in treating asymptomatic patients
  • May initiate treatment if the serum alkaline phosphatase (ALP) level is >2-4x the upper limit of normal (ULN) value

• Patients should receive adequate doses of Ca (1500 mg/day) and 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 and normalization of other bone turnover markers
  • Abnormal bone replacement with normal lamellar bone
  • Radiographic healing
  • Improvement in patient’s quality of life

Antiresorptive Therapy

Bisphosphonates

• Eg Alendronic acid, Etidronic acid, Pamidronic acid, Risedronic acid, Tiludronate, Zoledronic acid
• Inhibit osteoclast activity and decrease bone resorption
• Decrease bone pain, improve neurological complications, stabilize hearing loss, heal bone lesions
  • Biochemical effects: Decrease by 50% of serum ALP concentrations and urinary excretion of hydroxyproline, pyridinoline and collagen-derived N-telopeptides
  • Prolonged effectiveness; effects remain after years of withdrawal
  • Relatively safe with variable side effect profiles among different bisphosphonates

• Recommended for active Paget’s bone disease patients at risk of future complications and prior to surgery of pagetic bone
• Bisphosphonates may be used in patients presenting with fracture secondary to pagetic bone lesion
  • May be administered once the patient is stable

• Zoledronic acid is the most potent bisphosphonate approved in the United States for Paget’s bone disease
  • Biochemical remissions are sustained and can last up to 1-2 years in most patients
  • Preferred drug because of its efficacy especially in patients with more extensive disease and those who are already on several drug treatment for other conditions

• Pamidronic acid is an alternative intravenous agent but is less potent and takes longer to infuse compared with Zoledronic acid and some patients may develop drug resistance

• Risedronic acid is more effective than Etidronic acid
  • Preferred in younger patients with limited disease

• Alendronic acid is more effective than Pamidronic acid in patients previously treated with other bisphosphonates
  • Alendronic acid is also more effective than Etidronic acid
  • Also preferred in younger patients with limited disease

• Neridronate is a nitrogen-containing bisphosphonate with comparable efficacy to Zoledronic acid as shown in a randomized trial and can be given intravenously or intramuscularly but is available only in some countries

• Associated with possible risk of atypical subtrochanteric and diaphyseal femur fractures

Calcitonin

• 32 amino acid hormone secreted by C cells of the thyroid gland
• Inhibit osteoclast activity and decrease bone resorption
• Alternative for patients who cannot tolerate bisphosphonates or when bisphosphonates are contraindicated
• Decrease bone pain, improves neurological complications, stabilizes hearing loss, heals bone lesions
  • Biochemical effect: Up to 30-50% decrease in serum ALP and urinary hydroxyproline within 3-6 months and 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 with antipyretic properties

Nonsteroidal Anti-inflammatory Drugs (NSAIDs)

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

COX-2 Inhibitors

• Selective inhibition of COX-2 pathway without inhibiting COX-1 pathway
• Have analgesic, anti-inflammatory and antipyretic properties with reported improved gastrointestinal (GI) tolerance

Management of Complications of Paget's Disease of the Bone

Hearing loss

• It is suggested to use a potent bisphosphonate to prevent worsening of hearing deficit

Osteoarthritis

• The use of analgesics is suggested as an adjunctive therapy for mild-to-moderate joint pain caused by joint cartilage deterioration
• In patients with severe osteoarthritis, bisphosphonate therapy is recommended before undergoing elective total joint replacement

Paralysis

• Immediate treatment with a potent intravenous (IV) bisphosphonate is suggested along with neurosurgical consultation
• Due to correction of ischemia, most patients with paralysis recover well after medical therapy
• But in cases of severe structural damage, surgery may be required although the outcome may not be always optimal

Bowing of lower extremity

• A potent bisphosphonate prior to elective surgery is suggested on patients requiring an osteotomy to correct severe bowing of the lower extremity

Neoplasms

• Osteosarcoma or a giant cell tumor patients should be evaluated by an orthopedic surgeon
• For planned surgery, pretreatment with a potent bisphosphonate is suggested to reduce bleeding from adjacent pagetic bone

Congestive heart failure

• An effective treatment improves the symptoms
• Bisphosphonate treatment in patients with Paget's disease with congestive heart failure is recommended

Physical Therapy

• Improves muscle strength to help control certain types of pain
• Helps to maintain flexibility and joint range of motion, increase endurance and avoid deconditioning