Oral Presentation Annual Meetings of the Endocrine Society of Australia and Society for Reproductive Biology and Australia and New Zealand Bone and Mineral Society 2016

Cancer associated avascular necrosis of bone (#41)

Craig Munns 1
  1. Childrens Hospital at Westmead, Sydney, NSW, Australia

With increased survival rates of childhood and adult caner, the impact of long-term adverse effects of treatment are increasingly important. In paediatric acute lymphoblastic leukaemia (ALL), avascular necrosis (AVN) is a well-recognized complication of chemotherapy that significantly impacts long term quality of life. The Child hood cancer survivor study has compared the rate of self-reported AVN in cancer survivors with the rate observed in a sibling comparison group. The rate ratio was 6.5 in non-transplanted ALL, 11.2 in non-transplanted AML, and 59.2 for allogeneic hematopoietic stem cell transplantation (HSCT) recipients. Glucocorticoid use (prednisolone and dexamethasone) has been implicated as a major etiological factor in the development of ON in this patient group. Other risk factors include age >10 years, female sex, Caucasian race, and higher body mass index.4- 8 Some ALL treatment regimens have a much higher frequency of ON than others, suggesting that some non-glucocorticoid drugs (e.g., Asparaginase and methotrexate) may modify the risk of osteonecrosis. Multiple candidate genes studies and GWAS have indicated several polymorphisms in genes putatively related to the development of ON such as SERPINE1, VDR, CYP3A4, ACP1 and SH3YL1.

AVN in adults is reported in between 4 – 10% following cancer treatment. Hip is affected in 80% of cases followed by the knee at 10%. As with children, the outcome can be devastating with approximately 80% of subjects undergoing a hip replacement within 5 years of diagnosis. Risk factors in adults include glucorticoid exposure, total body irradiation, haematological malignancy and following BMT.

Routine management is centred on risk-factor reduction, symptomatic relief and eventual joint replacement. Maintenance of joint integrity with antiresorpive therapy has been investigated and will be expanded upon during the talk as will the possibility of enhancing anabolism within the area of AVN.