Abstract
High-dose methothrexate, a standard agent in the therapy protocols for osteosarcoma, has long been suspected to have a negative long-term effect on bone metabolism and bone mineral density, especially in children and young adults. Recent literature questioned this association as also the BMD of Ewing‘s sarcoma patients treated without methothrexate is known to be decreased. We therefore wanted to screen our patients treated for Ewing‘s sarcoma and osteosarcoma for osteopenia/osteoporosis-associated fractures.
Between 1994 and 2008 107 patients below 50y of age were treated for bone malignancies including 51 Ewing’s sarcomas – 31 male and 20 female – with a mean age at diagnosis of 17y(±11SD) and 56 osteosarcomas – 36 male and 20 female – with a mean age of 23y(±12SD). We screened the patients‘ files for fractures after chemotherapy.
We found five patients with not trauma-associated fractures – one Ewing‘s sarcoma(1/51;2%) and four osteosarcoma patients(4/56;7%). They presented one fracture of the proximal femur 107 months after tumour diagnosis, three fractures of the distal femur after 29, 51, and 72 months and two fractures of the proximal tibia after 29 and 32 months (one patient suffered from fractures affecting both – the distal femur and the proximal tibia).
As presented in our case series fractures due to an osteoporotic process after chemotherapy for bone sarcomas are well known late effects. Although described in several studies therapeutic recommendations for pro-phylaxis are sparse. Furthermore the fact that fractures occurred in both types of sarcoma casts MTX as the main cause of chemotherapy-induced osteoporosis into doubt. Additionally we estimate a high number of unreported cases of premature osteoporosis because sarcoma patients are usually not tested for their BMD-levels. Therefore further studies using DEXA (dual-energy-x-ray-absorptiometry) to measure the patients BMDs after chemotherapy are needed.
Correspondence should be addressed to Professor Stefan Bielack, Olgahospital, Klinikum Stuttgart, Bismarkstrasse 8, D-70176 Stuttgart, Germany. Email: s.bielack@klinikum_stuttgart.de