Late Effects of the Musculoskeletal System
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.
Most of our knowledge about cancer and its treatment effects on bone mineralization has been derived from studies of children with ALL.[24,33] In this group, the leukemic process, and possibly vitamin D deficiency, may play a role in the alterations in bone metabolism and bone mass observed at diagnosis. Antileukemic therapy causes further bone mineral density loss,  which has been reported to normalize over time [39,40] or to persist for many years after completion of therapy.[41,42] Clinical factors predicting higher risk for low bone mineral density include treatment with high cumulative doses of methotrexate (>40 g/m2), high cumulative doses of corticosteroids (>9 g/m2), and use of more potent glucocorticoids like dexamethasone.[41,43,44] Investigations evaluating the contribution of cranial radiation to the risk of low bone mineral density in childhood cancer survivors have yielded conflicting results.[41,45] Bone mineral density deficits that are likely multifactorial in etiology have been reported in allogeneic hematopoietic cell transplant recipients conditioned with TBI.[46,47] French investigators observed a significant risk for lower femoral bone mineral density among adult survivors of childhood leukemia treated with hematopoietic stem cell transplantation (HSCT) who had gonadal deficiency. Hormonal therapy has been shown to enhance bone mineral density of adolescent girls diagnosed with hypogonadism after HSCT.[Level of evidence: 3iiiC]