Bone Abstracts

Childhood cancer has become curable in the majority (>70%) of patients. This is mainly due to rising intensity of treatment, including (combinations of) surgery, chemotherapy, radiotherapy and stem cell transplantation. In addition, intensive international collaboration for rare subgroups, enhanced stratification for treatment regimens and optimised supportive care has contributed to the improved survival of pediatric cancer that was accomplished over the last decades.

Decreased bone mineral density and subsequent increased fracture risk is an important consequence of childhood cancer treatment in which substantial dosages and long-term administration steroids is required. Not only the total cumulative dosage (TCD), but also the type of steroids has been shown to be relevant. In addition, therapeutic agents, used for solid tumors such as ifosfamide are detrimental for bone turnover, directly or due to renal toxicity (Renal Fanconi). Recently, the use of the promising drug Imatinib, has shown to cause serious bone toxicity. Apart from treatment, the diseases itself (bone marrow infiltration), lymphokine production, immobilisation and general illness are obvious contributing factors for impaired bone mineral density. In addition, similar treatment can cause differenct bone toxicity in different individuals, suggesting a role for genetic variation, which has been confirmed by identifying several single nucleotide polymorphisms (SNPs) that predispose to a higher risk for osteopenia in childhood cancer.

Another important osteogenic complication of childhood cancer treatment is avascular bone necrosis or osteonecrosis (ON), which is especially observed in children suffering from acute lymphoblastic leukemia (ALL). Risk factors for developing this serious invalidating side effect are female gender and pubertal age. Also it has been show that treatment factors are important, and especially the individual combined steroids and asparaginase pharmacokinetics, seems to be the most important factor for the development of ON. In addition, also for ON, genetic variance is relevant. Avoidance of ON in a teenager with disease as ALL is a challenge, as treatment adjustment carries the risk of impaired survival.

As survival rates improve, the absolute number of childhood cancer survivors increases substantially, and late sequelae become increasingly important. Interestingly, avascular bone necrosis has been shown to be reversible in a substantial number of children that have survived childhood ALL. Long term effect studies as based on national survivor cohorts are currently being designed. Although it has been shown that most childhood cancer survivors reach normal peak bone mass in young adolescency, whether the risk of osteoporosis is increased in survivors reaching menopause, to be determined as the first cohorts of childhood cancer survivors now reach that era.