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Late Effects

Musculoskeletal

 

 

Etiology of Osteoporosis

 

Osteoporosis can occur after:

Treatment for solid tumors:

Causes:

  • Therapy:
    • Chemotherapy
      • Ifosfamide-induced Fanconi syndrome
        • Causes hypophosphatemia and severe metabolic bone disease
  • Nutritional disorders:
    • Malnutrition
    • Calcium and vitamin D deficiencies
    • Use of parenteral nutrition
  • Physical activity reduction during therapy:
    • Results in disuse osteoporosis
    • Reduced muscle mass results in decreased bone formation
  • Hormonal status:
    • Growth hormone levels
    • Pubertal status
  • Genetic factors:
    • Estimated that up to 80% of the variation in bone mass is (poly)genetically determined in healthy people


Treatment for leukemia:

Reduced BMD is a well known complication in children with ALL during treatment.

Most studies report normal BMD in survivors of childhood ALL treated without cranial RT.

Long term ALL survivors who had cranial radiation therapy (RT) may be at risk for developing osteoporosis (no clear relationship between BMD and growth hormone status though).

Growth may be impaired after cranial RT and children with short stature may be misclassified as having osteoporosis (it is important to correct BMD for height or calculate BMAD to correct for bone size).

Cause of reduced BMD in ALL is multifactorial:

  • Disease itself:
    • Leukemic infiltration of the bone damages the spongiosa structure
    • Various factors secreted by leukemic cells, such as ectopic production of parathyroid hormone (PTH) or PTH-related peptide, and paracrine secretion of lymphokines.
  • Therapy:
    • Corticosteroids
      • affect bone directly
      • alter hormonal axes
      • corticosteroids reduce intestinal calcium absorption and increase renal calcium excretion
    • Methotrexate
    • RT


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