Also, cranial radiation therapy damages the hypothalamic-pituitary axis (HPA) in an age- and dose-response fashion, often leading to growth hormone deficiency (GHD).[14,15] If untreated during the growing years, and sometimes, even with appropriate treatment, this leads to a substantially lower final height. Patients with a central nervous system (CNS) tumor [14,16] or acute lymphoblastic leukemia (ALL)[17,18,19] treated with 18 Gy or more of cranial radiation therapy are at highest risk. Also, patients treated with total-body irradiation (TBI), particularly single fraction TBI, are at risk of GHD.[20,21,22,23] In addition, if the spine is also irradiated (e.g., craniospinal radiation therapy for medulloblastoma or early ALL therapies in the 1960s), growth can be affected by two separate mechanisms—GHD and direct damage to the spine.
Amputation and limb-sparing surgery
Amputation and limb-sparing surgery prevent local recurrence of bone tumors by removal of all gross and microscopic disease. If optimally executed, both procedures accomplish an en bloc excision of tumor with a margin of normal uninvolved tissue. The type of surgical procedure, the primary tumor site, and the age of the patient affect the risk of postsurgical complications. Complications in survivors treated with amputation include stump-prosthetic problems, chronic stump pain, phantom limb pain, and bone overgrowth.[25,26] While limb-sparing surgeries may offer a more aesthetically pleasing outcome, complications have been reported more frequently in survivors undergoing these procedures compared with those treated with amputation. Complications after limb-sparing surgery include non-union, pathologic fracture, aseptic loosening, limb-length discrepancy, endoprosthetic fracture, poor joint movement, and stump-prosthesis problems.[25,27] Occasionally, refractory complications develop after limb-sparing surgery and require amputation.[28,29] A number of studies have compared functional outcomes after amputation and limb-sparing surgery, but results have been limited by inconsistent methods of functional assessment and small cohort sizes. Overall, data suggest that limb-sparing surgery results in better function than amputation, but differences are relatively modest.[25,29] Similarly, long-term quality of life outcomes among survivors undergoing amputation and limb sparing procedures have not differed substantially.
Hematopoietic cell transplantation with any history of chronic graft-versus-host disease is associated with joint contractures.[30,31,32]
Maximal peak bone mass is an important factor influencing the risk of osteoporosis and fracture associated with aging. Methotrexate has a cytotoxic effect on osteoblasts, resulting in a reduction of bone volume and formation of new bone.[33,34] This effect may be exacerbated by the chronic use of corticosteroids, another class of agents routinely used in the treatment of hematological malignancies and in supportive care for a variety of pediatric cancers. Radiation-related endocrinopathies, such as GHD or hypogonadism, may contribute to ongoing bone mineral loss.[35,36] In addition, suboptimal nutrition and physical inactivity may further predispose to deficits in bone mineral accretion.