The effect of chemotherapy on the growing skeleton

With the increasing use of high dose (poly)chemotherapy schedules in the treatment of childhood cancer it is particularly important to know the adverse effects of these treatments. Growth is a complex mechanism affected not only by chemotherapy but also by the malignancy itself as well as nutritional status, the use of corticosteroids and (cranial) radiation. In vitro and animal studies are often the most useful in determining the effect of a single chemotherapeutic agent on the growing skeleton. In vitro studies have shown doxorubicin, actinomycin D and cisplatin to have a direct effect on growth plate chondrocytes that in animals results in decreased growth and final height. Clinical studies with multiagent chemotherapy have demonstrated that antimetabolites decrease bone growth and final height. Childhood cancer survivors are at risk of a reduced bone mineral density, mainly due to methotrexate, ifosfamide and corticosteroids. This reduced bone mineral density persists into adult life and may increase bone fracture risk at an older age.