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Late Effects of the Musculoskeletal System


Osteonecrosis is more common in adolescents than in children, with the highest risk among those who are older than 10 years.[61,62,66,67] Osteonecrosis also occurs much more frequently in whites than in blacks.[65,66] Studies evaluating the influence of gender on the risk of osteonecrosis have yielded conflicting results, with some suggesting a higher incidence in females [55,66,67] that has not been confirmed by others.[53,55,62] Genetic factors influencing antifolate and glucocorticoid metabolism have also been linked to excess risk of osteonecrosis among survivors.[65] St. Jude Children's Research Hospital investigators observed an almost sixfold (odds ratio = 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.[61]


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.[68] 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.[69] Growth hormone therapy may influence the onset and pace of growth of osteochondromas.[23,70] 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.[71]

Table 13. Bone and Joint Late Effects

Predisposing TherapyMusculoskeletal EffectsHealth Screening
CT = computed tomography; DXA = dual-energy x-ray absorptiometry; GVHD = graft-versus-host disease; HSCT = hematopoietic stem cell transplantation.
Radiation impacting musculoskeletal systemHypoplasia; fibrosis; reduced/uneven growth (scoliosis, kyphosis); limb length discrepancyExam: bones and soft tissues in radiation fields
Radiation impacting head and neckCraniofacial abnormalitiesHistory: psychosocial assessment, with attention to: educational and/or vocational progress, depression, anxiety, post-traumatic stress, social withdrawal
Head and neck exam
Radiation impacting musculoskeletal systemRadiation-induced fractureExam of affected bone
Methotrexate; corticosteroids (dexamethasone, prednisone); radiation impacting skeletal structures; HSCTReduced bone mineral densityBone mineral density test (DXA or quantitative CT)
Corticosteroids (dexamethasone, prednisone)OsteonecrosisHistory: joint pain, swelling, immobility, limited range of motion
Musculoskeletal exam
Radiation with impact to oral cavityOsteoradionecrosisHistory/oral exam: impaired or delayed healing following dental work, persistent jaw pain or swelling, trismus
HSCT with any history of chronic GVHDJoint contractureMusculoskeletal exam
AmputationAmputation-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 surgeryLimb-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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