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    Late Effects of Treatment for Childhood Cancer (PDQ®): Treatment - Health Professional Information [NCI] - Late Effects of the Musculoskeletal System

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    Osteonecrosis is more common in adolescents than in children, with the highest risk among those who are older than 10 years.[62,63,67,68] Osteonecrosis also occurs much more frequently in whites than in blacks.[66,67] Studies evaluating the influence of gender on the risk of osteonecrosis have yielded conflicting results, with some suggesting a higher incidence in females [56,67,68] that has not been confirmed by others.[54,56,63] Genetic factors influencing antifolate and glucocorticoid metabolism have also been linked to excess risk of osteonecrosis among survivors.[66] St. Jude Children's Research Hospital investigators observed an almost sixfold (OR, 5.6; 95% confidence interval [CI], 2.7-11.3) risk of osteonecrosis among survivors with polymorphism of the ACP1 gene, which regulates lipid levels and osteoblast differentiation.[62]

    Osteochondroma

    Approximately 5% of children undergoing myeloablative stem cell transplantation will develop osteochondroma, a benign bone tumor that most commonly presents in the metaphyseal regions of long bones. Osteochondroma generally occurs as a single lesion, however multiple lesions may develop in the context of hereditary multiple osteochondromatosis.[69] A large Italian study reported a 6.1% cumulative risk of developing osteochondroma at 15 years posttransplant, with increased risk associated with younger age at transplant (≤3 yrs) and use of TBI.[70] Growth hormone therapy may influence the onset and pace of growth of osteochondromas.[23,71] Because malignant degeneration of these lesions is exceptionally rare, clinical rather than radiological follow-up is most appropriate, and surgery for biopsy or resection is generally unnecessary.[72]

    Table 13. Bone and Joint Late Effects

    Predisposing Therapy Musculoskeletal Effects Health Screening
    CT = computed tomography; DXA = dual-energy x-ray absorptiometry; GVHD = graft-versus-host disease; HSCT = hematopoietic stem cell transplantation.
    Radiation impacting musculoskeletal system Hypoplasia; fibrosis; reduced/uneven growth (scoliosis, kyphosis); limb length discrepancy Exam: bones and soft tissues in radiation fields
    Radiation impacting head and neck Craniofacial abnormalities History: psychosocial assessment, with attention to: educational and/or vocational progress, depression, anxiety, posttraumatic stress, social withdrawal
    Head and neck exam
    Radiation impacting musculoskeletal system Radiation-induced fracture Exam of affected bone
    Methotrexate; corticosteroids (dexamethasone, prednisone); radiation impacting skeletal structures; HSCT Reduced bone mineral density Bone mineral density test (DXA or quantitative CT)
    Corticosteroids (dexamethasone, prednisone) Osteonecrosis History: joint pain, swelling, immobility, limited range of motion
    Musculoskeletal exam
    Radiation with impact to oral cavity Osteoradionecrosis History/oral exam: impaired or delayed healing after dental work, persistent jaw pain or swelling, trismus
    HSCT with any history of chronic GVHD Joint contracture Musculoskeletal exam
    Amputation Amputation-related complications (impaired cosmesis, functional/activity limitations, residual limb integrity, chronic pain, increased energy expenditure) History: pain, functional/activity limitations
    Exam: residual limb integrity
    Prosthetic evaluation
    Limb-sparing surgery Limb-sparing surgical complications (functional/activity limitations, fibrosis, contractures, chronic infection, chronic pain, limb length discrepancy, increased energy expenditure, prosthetic malfunction [loosening, non-union, fracture]) History: pain, functional/activity limitations
    Exam: residual limb integrity
    Radiograph of affected limb
    Orthopedic evaluation
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