Musculoskeletal
Etiology
Musculoskeletal problems can be related to many factors after treatment for childhood cancer:
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Systemic therapy
Radiation Therapy (RT)
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Nutritional disorders
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Reduced physical activity during illness
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Endocrine disorders
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The underlying cancer
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Genetic factors
Systemic therapy:
- Chemotherapy
- Steroids:
- Glucocorticoids are integral part of the therapy for leukemia and lymphoma
- Cause decreased bone mass
Radiation Therapy (RT):
RT causes reduced growth of all the bones and soft tissues included in the RT field in a growing child.
The extent of this damage will depend on:
- Age of the child at the time of treatment
- The younger the child, the more severe the effect will be
- Total dose of RT given
- Extent of the RT treatment field
- The larger the treatment field, the greater the extent of the damage
- Treatment may cover areas where more growth is likely to occur and so the effect is more damaging
- Fractionation schedule of the RT (how it is split up - larger fractions associated with more damage)
- Quality of the radiotherapy
- Low energy (orthovoltage) RT is absorbed significantly more in bone than higher energy RT. This results in an increased dose within bone and increased damage.
- Low energy (orthovoltage) RT is absorbed significantly more in bone than higher energy RT. This results in an increased dose within bone and increased damage.
Nutritional disorders:
Malnutrition
- Calcium and vitamin D deficiencies
- Use of parenteral nutrition
Reduction in physical activity during therapy:
- Results in disuse osteoporosis
- Reduced muscle mass results in decreased bone formation
Endocrine deficiencies:
- Growth hormone deficiency
- Sex steroid deficiency
- Hypogonadism both in males and females
The underlying cancer:
Acute lymphoblastic leukemia (ALL) can itself cause skeletal abnormalities.
Bone sarcomas damage the integrity of the underlying bone and predispose to pathological fracture.
Genetic factors:
Estimated that up to 80% of the variation in bone mass is (poly)genetically determined in healthy people.
Candidate polymorphisms are in the vitamin D receptor gene, the collagen I A1 gene and the estrogen receptor gene.
Recently reported that single nucleotide polymorphisms of the methylenetetrahydrofolate reductase gene (MTHFR; C677T and A1298C), methionine synthase reductase gene (MTRR; A66G), and vitamin D receptor gene are important determinants of osteoporosis in pediatric ALL patients.
Polymorphisms in the glucocorticoid receptor may cause differences in BMD and body mass index among the genotypes in healthy adults. Differences in glucocorticoid sensitivity may explain variation in side-effects.
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