Pathobiology and Prevention of Cancer Chemotherapy-Induced Bone Growth Arrest, Bone Loss, and Osteonecrosis

C.      Fan; B.      K. Foster; W.      H. Wallace; C.      J. Xian

Abstract

Cancer chemotherapy has been recognized as one severe risk factor that influences bone growth and bone mass accumulation during childhood and adolescence. This article reviews on the importance of this clinical issue, current understanding of the underlying mechanisms for the skeletal defects and potential preventative strategies. Both clinical and basic studies that appeared from 1990 to 2010 were reviewed for bone defects (growth arrest, bone loss, osteonecrosis, and/or fractures) caused by paediatric cancer chemotherapy. As chemotherapy has become more intensive and achieved greater success in treating paediatric malignancies, skeletal complications such as bone growth arrest, low bone mass, osteonecrosis, and fractures during and/or after chemotherapy have become a problem for some cancer patients and survivors particularly those that have received high dose glucocorticoids and methotrexate. While chemotherapy-induced skeletal defects are likely multi-factorial, recent studies suggest that different chemotherapeutic agents can directly impair the activity of the growth plate and metaphysis (the two major components of the bone growth unit) through different mechanisms, and can alter bone modeling/remodeling processes via their actions on bone formation cells (osteoblasts), bone resorption cells (osteoclasts) and bone “maintenance” cells (osteocytes). Intensive use of multi-agent chemotherapy can cause growth arrest, low bone mass, fractures, and/or osteonecrosis in some paediatric patients. While there are currently no specific strategies for protecting bone growth during childhood cancer chemotherapy, regular BMD monitoring and exercise are have been recommended, and possible adjuvant treatments could include calcium/vitamin D, antioxidants, bisphosphonates, resveratrol, and/or folinic acid.

Keywords: Chemotherapy, childhood cancers, growth plate, bone mass, chondrocytes, osteoblasts, adipocytes, osteocytes, osteoclasts, bone marrow progenitor cells, methotrexate, glucocorticoids, growth defects, osteoporosis, osteopenia, osteonecrosis, bone loss, fractures, oxidative stress, prevention, bisphosphonates, calcium, vitamin D, folinic acid, antioxidants