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Diseases

Osteosarcoma

OVERVIEW

  • Highlights & Basics
  • Images

DIAGNOSIS

  • Diagnostic Approach
  • Risk Factors
  • History & Exam
  • Tests
  • Differential Diagnosis
  • Criteria
  • Screening

TREATMENT

  • Tx Approach
  • Tx Options
  • Emerging Tx
  • Prevention

FOLLOW-UP

  • Overview
  • Complications

REFERENCES

  • Citations
  • Guidelines
  • Credits

PATIENT RESOURCES

  • Patient Instructions

Highlights & Basics

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Key Highlights
  • Osteosarcoma is the most common nonhematologic primary malignant neoplasm of bone in children and adolescents.

  • Pain and swelling are the most common presenting symptoms.

  • Although it can occur at any age, it usually affects patients in the second and third decade of life with a peak incidence between 13 and 16 years of age. It is more common in males than females.

  • Chemotherapy combined with surgery is the standard of care.

  • Prognosis of patients with localized disease has improved substantially following the introduction of chemotherapy, with 75% to 80% 5-year survival rates.

Quick Reference

  • History & Exam

    • Key Factors

      • Other Factors

        More information...
      • Diagnostics Tests

          More information...
        • Treatment Options

            More information...

          Definition

          Epidemiology

          Etiology

          Pathophysiology

          content by BMJ Group
          Last updated

          Images

          • Conventional radiograph, anteroposterior view; poorly circumscribed, permeative lesion involving dis

            Conventional radiograph, anteroposterior view; poorly circumscribed, permeative lesion involving distal femoral metaphysis with mixed radiodense and radiolucent appearance; a large soft tissue mass with periosteal reaction is also present

          • Computed tomographic scan, axial view; osteosarcoma of proximal tibia; matrix production and bone de

            Computed tomographic scan, axial view; osteosarcoma of proximal tibia; matrix production and bone destruction are best appreciated on conventional tomographs

          • Magnetic resonance imaging, coronal view; osteosarcoma of distal femur showing low-intensity signal;

            Magnetic resonance imaging, coronal view; osteosarcoma of distal femur showing low-intensity signal; T1-weighted image; actual intraosseous and extraosseous tumor extent is also appreciated

          • Magnetic resonance imaging, axial view; osteosarcoma of distal femur showing high-intensity signal;

            Magnetic resonance imaging, axial view; osteosarcoma of distal femur showing high-intensity signal; T2-weighted image

          • Bone scan; high radionuclide uptake at tumor site

            Bone scan; high radionuclide uptake at tumor site

          • Osteoblastic osteosarcoma; lace-like osteoid in a highly pleomorphic sarcomatous stroma

            Osteoblastic osteosarcoma; lace-like osteoid in a highly pleomorphic sarcomatous stroma

          Citations

            Key Articles

            • WHO Classification of Tumours Editorial Board. Soft tissue and bone tumours: WHO classification of tumours. 5th ed. vol 3. Lyon, France: IARD Press; 2020

            • National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: bone cancer [internet publication].[Full Text]

            • Strauss SJ, Frezza AM, Abecassis N, et al. Bone sarcomas: ESMO-EURACAN-GENTURIS-ERN PaedCan Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol. 2021 Dec;32(12):1520-36.[Abstract][Full Text]

            Other Online Resources

            • ​NIH, SEER: Cancer stat facts: bone and joint cancer
            • American Cancer Society: key statistics about bone cancer

            Referenced Articles

            • 1. WHO Classification of Tumours Editorial Board. Soft tissue and bone tumours: WHO classification of tumours. 5th ed. vol 3. Lyon, France: IARD Press; 2020

            • 2. Azar FM, Canale ST, Beaty JH. Campbell's operative orthopedics. 14th ed. Philadelphia, PA: Elsevier; 2021. 

            • 3. Cole S, Gianferante DM, Zhu B, et al. Osteosarcoma: a surveillance, epidemiology, and end results program-based analysis from 1975 to 2017. Cancer. 2022 Jun 1;128(11):2107-18.[Abstract][Full Text]

            • 4. Rojas GA, Hubbard AK, Diessner BJ, et al. International trends in incidence of osteosarcoma (1988-2012). Int J Cancer. 2021 Sep 1;149(5):1044-53.[Abstract][Full Text]

            • 5. Gianferante DM, Moore A, Spector LG, et al. Genetically inferred birthweight, height, and puberty timing and risk of osteosarcoma. Cancer Epidemiol. 2024 Oct;92:102432.[Abstract][Full Text]

            • 6. NCD Risk Factor Collaboration (NCD-RisC). Height and body-mass index trajectories of school-aged children and adolescents from 1985 to 2019 in 200 countries and territories: a pooled analysis of 2181 population-based studies with 65 million participants. Lancet. 2020 Nov 7;396(10261):1511-24.[Abstract][Full Text]

            • 7. NCD Risk Factor Collaboration (NCD-RisC). A century of trends in adult human height. Elife. 2016 Jul 26;5:e13410.[Abstract][Full Text]

            • 8. Good DA, Busfield F, Fletcher BH, et al. Linkage of Paget disease of bone to a novel region on human chromosome 18q23. Am J Hum Genet. 2002 Feb;70(2):517-25.[Abstract][Full Text]

            • 9. Hansen MF, Nellissery MJ, Bhatia P. Common mechanisms of osteosarcoma and Paget's disease. J Bone Miner Res. 1999 Oct;14 Suppl 2:39-44.[Abstract]

            • 10. Nellissery MJ, Padalecki SS, Brkanac Z, et al. Evidence for a novel osteosarcoma tumor-suppressor gene in the chromosome 18 region genetically linked with Paget disease of bone. Am J Hum Genet. 1998 Sep;63(3):817-24.[Abstract][Full Text]

            • 11. Le Vu B, de Vathaire F, Shamsaldin A, et al. Radiation dose, chemotherapy and risk of osteosarcoma after solid tumours during childhood. Int J Cancer. 1998 Jul 29;77(3):370-7.[Abstract]

            • 12. Schwartz B, Benadjaoud MA, Cléro E, et al. Risk of second bone sarcoma following childhood cancer: role of radiation therapy treatment. Radiat Environ Biophys. 2014 May;53(2):381-90.[Abstract][Full Text]

            • 13. Hawkins MM, Wilson LM, Burton HS, et al. Radiotherapy, alkylating agents, and risk of bone cancer after childhood cancer. J Natl Cancer Inst. 1996 Mar 6;88(5):270-8.[Abstract]

            • 14. Campanacci M. Bone and soft tissue tumors: clinical features, imaging, pathology and treatment. 2nd ed. New York, NY: Springer; 1999.

            • 15. Troisi R, Masters MN, Joshipura K, et al. Perinatal factors, growth and development, and osteosarcoma risk. Br J Cancer. 2006 Dec 4;95(11):1603-7.[Abstract][Full Text]

            • 16. Martin JW, Squire JA, Zielenska M. The genetics of osteosarcoma. Sarcoma. 2012;2012:627254.[Abstract][Full Text]

            • 17. Yamaguchi T, Toguchida J, Yamamuro T, et al. Allelotype analysis in osteosarcomas: frequent allele loss on 3q, 13q, 17p, and 18q. Cancer Res. 1992 May 1;52(9):2419-23.[Abstract][Full Text]

            • 18. Overholtzer M, Rao PH, Favis R, et al. The presence of p53 mutations in human osteosarcomas correlates with high levels of genomic instability. Proc Natl Acad Sci U S A. 2003 Sep 30;100(20):11547-52.[Abstract][Full Text]

            • 19. Miller CW, Aslo A, Won A, et al. Alterations of the p53, Rb and MDM2 genes in osteosarcoma. J Cancer Res Clin Oncol. 1996;122(9):559-65.[Abstract]

            • 20. Mirabello L, Yeager M, Mai PL, et al. Germline TP53 variants and susceptibility to osteosarcoma. J Natl Cancer Inst. 2015 Jul;107(7):djv101.[Abstract][Full Text]

            • 21. Mirabello L, Zhu B, Koster R, et al. Frequency of pathogenic germline variants in cancer-susceptibility genes in patients with osteosarcoma. JAMA Oncol. 2020 May 1;6(5):724-34.[Abstract][Full Text]

            • 22. Wang LL, Gannavarapu A, Kozinetz CA, et al. Association between osteosarcoma and deleterious mutations in the RECQL4 gene in Rothmund-Thomson syndrome. J Natl Cancer Inst. 2003 May 7;95(9):669-74.[Abstract]

            • 23. National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: bone cancer [internet publication].[Full Text]

            • 24. Expert Panel on Musculoskeletal Imaging, Ahlawat S, Lenchik L, et al. ACR appropriateness criteria® suspected primary bone tumors: 2024 update. J Am Coll Radiol. 2025 May;22(5s):S440-54.[Abstract][Full Text]

            • 25. Letson D, Falcone R, Muro-Cacho C. Pathologic and radiologic features of primary bone tumors. Cancer Control. 1999 May;6(3):283-93.[Abstract]

            • 26. Strauss SJ, Frezza AM, Abecassis N, et al. Bone sarcomas: ESMO-EURACAN-GENTURIS-ERN PaedCan Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol. 2021 Dec;32(12):1520-36.[Abstract][Full Text]

            • 27. Malawer MM, Sugarbaker PH. Musculoskeletal cancer surgery: treatment of sarcomas and allied diseases. Dordrecht: Kluwer Academic Publishers; 2001.

            • 28. Meyer JS, Nadel HR, Marina N, et al. Imaging guidelines for children with Ewing sarcoma and osteosarcoma: a report from the Children's Oncology Group Bone Tumor Committee. Pediatr Blood Cancer. 2008 Aug;51(2):163-70.[Abstract]

            • 29. Letson D, Falcone R, Muro-Cacho C. Pathologic and radiologic features of primary bone tumors. Cancer Control. 1999;6:283-293.[Abstract]

            • 30. Mirabello L, Troisi RJ, Savage SA. Osteosarcoma incidence and survival rates from 1973 to 2004: data from the Surveillance, Epidemiology, and End Results Program. Cancer. 2009 Apr 1;115(7):1531-43.[Abstract][Full Text]

            • 31. Heck RK Jr, Peabody TD, Simon MA. Staging of primary malignancies of bone. CA Cancer J Clin. 2006 Nov-Dec;56(6):366-75.[Abstract][Full Text]

            • 32. Amin MB, Edge S, Greene F, et al. AJCC cancer staging manual, 8th edition. New York: Springer; 2016.

            • 33. American College of Radiology. ACR appropriateness criteria: malignant or aggressive primary musculoskeletal tumor-staging and surveillance. 2022 [internet publication].[Full Text]

            • 34. Ferrari S, Ruggieri P, Cefalo G, et al. Neoadjuvant chemotherapy with methotrexate, cisplatin, and doxorubicin with or without ifosfamide in nonmetastatic osteosarcoma of the extremity: an Italian sarcoma group trial ISG/OS-1. J Clin Oncol. 2012 Jun 10;30(17):2112-8.[Abstract]

            • 35. Marina NM, Smeland S, Bielack SS, et al. Comparison of MAPIE versus MAP in patients with a poor response to preoperative chemotherapy for newly diagnosed high-grade osteosarcoma (EURAMOS-1): an open-label, international, randomised controlled trial. Lancet Oncol. 2016 Oct;17(10):1396-408.[Abstract][Full Text]

            • 36. Anderson ME. Update on survival in osteosarcoma. Orthop Clin North Am. 2016 Jan;47(1):283-92.[Abstract]

            • 37. Davis LE, Bolejack V, Ryan CW, et al. Randomized double-blind phase II study of regorafenib in patients with metastatic osteosarcoma. J Clin Oncol. 2019 Jun 1;37(16):1424-31.[Abstract][Full Text]

            • 38. American College of Rheumatology. 2022 American College of Rheumatology (ACR) guideline for vaccinations in patients with rheumatic and musculoskeletal diseases. Feb 2023 [internet publication].[Full Text]

            • 39. Haanen J, Obeid M, Spain L, et al. Management of toxicities from immunotherapy: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol. 2022 Dec;33(12):1217-38.[Abstract][Full Text]

            • 40. Bielack SS, Kempf-Bielack B, Delling G, et al. Prognostic factors in high-grade osteosarcoma of the extremities and trunk: an analysis of 1,702 patients treated on neoadjuvant cooperative osteosarcoma study group protocols. J Clin Oncol. 2002 Feb 1;20(3):776-90.[Abstract]

            • 41. Hendershot E, Pappo A, Malkin D, et al. Tumor necrosis in pediatric osteosarcoma: impact of modern therapies. J Pediatr Oncol Nurs. 2006 Jul-Aug;23(4):176-81.[Abstract]

            • 42. Beird HC, Bielack SS, Flanagan AM, et al. Osteosarcoma. Nat Rev Dis Primers. 2022 Dec 8;8(1):77.[Abstract]

            • 43. Ferguson WS, Goorin AM. Current treatment of osteosarcoma. Cancer Invest. 2001;19:292-315.[Abstract]

            • 44. Kager L, Zoubek A, Kastner U, et al. Primary metastatic osteosarcoma: presentation and outcome of patients treated on neoadjuvant Cooperative Osteosarcoma Study Group protocols. J Clin Oncol. 2003 May 15;21(10):2011-8.[Abstract]

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