Osteosarcoma


Osteosarcoma – An Evaluation of Current Diagnosis, Treatment and Chemotherapy


Bahtiyar Demiralp,1 Gobinda Sarkar,1,3 Scott H Okuno,4 Michael J Yaszemski1,2 and Avudaiappan Maran1


1. Department of Orthopedic Surgery; 2. Department of Biomedical Engineering; 3. Department of Laboratory Medicine and Pathology; 4. Department of Oncology, Mayo Clinic, Rochester


Abstract


Osteosarcoma is a bone tumour that most often affects children and young adults. Although a combination of surgery to remove the primary tumour and chemotherapy prior to and after the surgery has led to an improved survival rate, local recurrence and metastases still develop in two-fifths of patients. A definitive therapy is yet to be determined for this deadly disease. This article discusses the current status on diagnosis and treatment, with an emphasis on developing new molecularly targeted therapies.


Keywords Bone tumour, chemotherapy, osteosarcoma, sarcoma, tumour surgery, 2-methoxyestradiol


Disclosure: The authors have no conflicts of interest to declare. Received: 6 May 2010 Accepted: 10 December 2010 Citation: European Musculoskeletal Review, 2011;6(1):18–23 Correspondence: Avudaiappan Maran, Mayo Clinic, 200 First Street SW, MS 3-69, Rochester MN 55905, US. E: maran.avudaiappan@mayo.edu


Osteosarcoma is the most common malignant primary bone tumour in children and adolescents. It is the sixth leading cancer in children >15 years of age. There are approximately 400 new cases each year in the US.1,2


The second peak for osteosarcoma is


American Joint Committee on Cancer is based on tumour grade, size and the presence and location of metastases (see Table 1).12


Osteosarcoma affects males more frequently than females, with a ratio of 1.6:1. It occurs early in females due to the earlier onset of growth spurt.3–5


between the sixth and eighth decades. The pathogenesis is still unclear, although several factors have been proposed. The standard clinical treatment consists of a combination of surgery and chemotherapy. There is limited knowledge, however, on how different types of surgery (limb salvage versus amputation), chemotherapy (pre- and post-operative) or other treatments (e.g. radiotherapy) influence the outcome.1


Osteosarcoma has been reported to occur in all bones of the body. It has an affinity with the metaphyseal portions of the long bones. It is commonly localised in the distal femur and proximal tibia region, which was observed in 973 out of 1,649 cases in a study carried out at the Mayo Clinic in Rochester.6


plates with higher proliferative activity and turnover of bone.7


These sites generally contain growth The next


most common location is the proximal humerus. It also rarely affects the bones of the hands and wrists.


In the group of axial locations of osteosarcoma, pelvic osteosarcomas account for approximately 7–9% of all osteosarcomas.3 osteosarcomas occur in 0.85–3% of cases.9


Spine Osteosarcoma occasionally arises in the soft tissue, thyroid gland, heart, kidney, uterus and lung.3,10


A staging system described by Enneking, which has been further accepted by the Musculoskeletal Tumor Society, divides all bone tumours including osteosarcoma into three stages based on grade, as described in Table 1.11


Another staging system described by the 18 Aetiology


Although it is likely that osteosarcoma arises from the osteoprogenitor cells, given its ability to form bone it is unclear at present what the cell of origin is for osteosarcoma. Recent findings have implicated mesenchymal stem cells as possible progenitors.13


These data are far


from definitive, however, and additional work will be needed to further confirm and define these results.


Transforming growth factor-β, a known inhibitor of the Rb gene, is elevated in high-grade osteosarcoma compared with low-grade osteosarcoma.3,14 these tumours.


It may contribute to the aggressive behaviour of


Many studies have shown a correlation between the faster rate of bone growth in puberty and occurrence of osteosarcoma.13


Additional


studies point out that young osteosarcoma patients are taller than the normal population of the same age group.15,16


Preceding trauma has


been proposed as a causative factor in some osteosarcoma cases; however, no evidence-based aetiological relationship with trauma has been established.3,17


Other predisposing factors include exposure to ionising radiation and a history of metabolic bone diseases (i.e. Paget’s disease).1,12


Radiation


is the proven risk factor in osteosarcoma, but it is rare and occurs after a long period of time has passed.18


be associated with a higher incidence of adult osteosarcoma.6


Co-existence of osteosarcoma with a number of rare inherited syndromes – such as Bloom syndrome, Rothmund-Thomson syndrome


© TOUCH BRIEFINGS 2011 Paget’s disease is known to


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