Approach to Diagnosis and Management of Osteosarcoma


  • Lisa Setia Waty Department of Orthopaedics and Traumatology, Sebelas Maret University, Surakarta, Indonesia
  • Rhyan Darma Saputra Sebelas Maret University
  • Dita Anggara Kusuma Consultant of Orthopaedics and Traumatology, Dr. Moewardi General Hospital, Surakarta, Indonesia



primary bone tumors:, malignant:, osteosarcoma:


In children and adolescents, osteosarcoma is a primary bone malignancy of mesenchymal origin. Osteosarcoma also occurs in an older age spectrum (>65 years) because of its association with abnormal bone growth as seen in Paget disease. At a younger age, the incidence of osteosarcoma is associated with rapid bone growth in adolescents. Although the pathophysiology is related to several factors, the exact cause is still unknown. Survival rates are expected to improve with treatment consisting of a combination or one of recently developed surgical resection, chemotherapy, and targeted immunotherapy. In this review article, we focus on the etiology and pathogenesis associated with the diagnosis and short-term and long-term management of osteosarcoma, including newly identified agents such as targeted immunotherapy.1,2


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Jafari F, Javdansirat S, Sanaie S, Naseri A, Shamekh A, Rostamzadeh D, et al. Osteosarcoma: A comprehensive review of management and treatment strategies. Vol. 49, Annals of Diagnostic Pathology. W.B. Saunders; 2020.

Misaghi A, Goldin A, Awad M, Kulidjian AA. Osteosarcoma: A comprehensive review. Vol. 4, SICOT-J. EDP Sciences; 2018.

Ottaviani G, Jaffe N. The epidemiology of osteosarcoma. In: Cancer Treatment and Research. Kluwer Academic Publishers; 2009. p. 3–13.

Mahyudin F, Edward M, Hardian Basuki M, Abdul Bari Y, Suwandani Y, Author C. HOSPITAL SURABAYA 'A RETROSPECTIVE STUDY'. 2018;(1). Available from:


Hameed M, Mandelker D. Tumor Syndromes Predisposing to Osteosarcoma. Vol. 25, Advances in Anatomic Pathology. Lippincott Williams and Wilkins; 2018. p. 217–22.

Fuchs B, Pritchard DJ. TUMOR BIOLOGY Etiology of Osteosarcoma [Internet]. Vol. 397, CLINICAL ORTHOPAEDICS AND RELATED RESEARCH Number. 2002. Available from:

Papalas JA, Balmer NN, Wallace C, Sangüeza OP. Ossifying Dermatofibroma With Osteoclast-Like Giant Cells: Report of a Case and Literature Review [Internet]. Available from:

Widhe B, Widhe T. Initial Symptoms and Clinical Features in Osteosarcoma and Ewing Sarcoma*. JBJS [Internet]. 2000;82(5). Available from:

Kundu ZS. Classification, imaging, biopsy and staging of osteosarcoma. In: Indian Journal of Orthopaedics. Medknow Publications; 2014. p. 238–46.

Fu Y, Lan T, Cai H, Lu A, Yu W. Meta-analysis of serum lactate dehydrogenase and prognosis for osteosarcoma. Medicine. 2018 May;97(19):e0741.

Yakushiji T, Oka K, Sato H, Yorimitsu S, Fujimoto T, Yamashita Y, et al. Characterization of chondroblastic osteosarcoma: Gadolinium-enhanced versus diffusion-weighted MR imaging. Journal of Magnetic Resonance Imaging. 2009 Apr;29(4):895–900.

Brenner W, Bohuslavizki KH, Eary JF. PET Imaging of Osteosarcoma* [Internet]. Available from:

Misaghi A, Goldin A, Awad M, Kulidjian AA. Osteosarcoma: A comprehensive review. Vol. 4, SICOT-J. EDP Sciences; 2018.

Kaseta MKA, Gomatos IP, Khaldi L, Tzagarakis GP, Alevizos L, Themistocleous GS, et al. Prognostic Value of Bax, Cytochrome c, and Caspase-8 Protein Expression in Primary Osteosarcoma. Hybridoma. 2007 Dec;26(6):355–62.

Yalçın B, Gedikoğlu G, Kutluk T, Varan A, Akyüz C, Büyükpamukçu M. C-erbB-2 expression and prognostic significance in osteosarcoma. Pediatric Blood Cancer. 2008 Aug;51(2):222–7.

Zhao CH, Li QF, Chen LY, Tang J, Song JY, Xie Z. [Expression and localization of hnRNP A2/B1 during differentiation of human osteosarcoma MG-63 cells induced by HMBA]. Ai Zheng. 2008 Jul;27(7):677–84.

Luo X, Chen J, Song WX, Tang N, Luo J, Deng ZL, et al. Osteogenic BMPs promote tumor growth of human osteosarcomas that harbor differentiation defects. Laboratory Investigation. 2008 Dec;88(12):1264–77.

Sandhu R, Lal H, Kundu ZS, Kharb S. Serum Fluoride and Sialic Acid Levels in Osteosarcoma. Biol Trace Elem Res. 2011 Dec 24;144(1–3):1–5.

GUO W, ZHAO S, YU L, TANG J, WU G, CHEN J. Expression and its clinical significance of heat shock protein gp96 in human osteosarcoma. Neoplasma. 2010 Jan;57(1):62–7.

Babkina I v., Osipov DA, Solovyov YuN, Bulycheva I v., Machak GN, Aliev MD, et al. Endostatin, Placental Growth Factor, and Fibroblast Growth Factors-1 and -2 in the Sera of Patients with Primary Osteosarcomas. Bull Exp Biol Med. 2009 Aug 10;148(2):246–9.

YU L, GUO WC, ZHAO SH, TANG J, CHEN JL. Mitotic arrest defective protein 2 expression abnormality and its clinicopathologic significance in human osteosarcoma. APMIS. 2010 Mar;118(3):222–9.

Zhang Z, Qiu Y, Hua Y, Wang Y, Chen T, Zhao A, et al. Serum and Urinary Metabonomic Study of Human Osteosarcoma. J Proteome Res. 2010 Sep 3;9(9):4861–8.

Xu J, Wu S, Shi X. Expression of matrix metalloproteinase regulator, RECK, and its clinical significance in osteosarcoma. Journal of Orthopaedic Research. 2010 Dec;28(12):1621–5.

Baumhoer D, Elsner M, Smida J, Zillmer S, Rauser S, Schoene C, et al. CRIP1 expression is correlated with a favorable outcome and less metastases in osteosarcoma patients. Oncotarget. 2011 Dec 31;2(12):970–5.

Shimizu T, Ishikawa T, Iwai S, Ueki A, Sugihara E, Onishi N, et al. Fibroblast Growth Factor-2 Is an Important Factor that Maintains Cellular Immaturity and Contributes to Aggressiveness of Osteosarcoma. Molecular Cancer Research. 2012 Mar 1;10(3):454–68.

Klein MJ, Siegal GP. Osteosarcoma: Anatomic and histologic variants. Vol. 125, American Journal of Clinical Pathology. American Society of Clinical Pathologists; 2006. p. 555–81.

Pan Y, Chen D, Hu T, Lv G, Dai Z. Characteristics and Prognostic Factors of Patients With Osteosarcoma Older Than 60 Years From the SEER Database. Cancer Control. 2019 Jan 1;26(1):107327481988889.

Pahade J, Sekhar A, Shetty SK. Imaging of Malignant Skeletal Tumors. Vol. 367. 2008.

Moore DD, Luu HH. Osteosarcoma. Cancer Treat Res. 2014;162:65–92.

William Enneking BF, Spanier SS, Goodman MA. Current Concepts Review The Surgical Staging of Musculoskeletal Sarcoma*. 1980.

Edge SB, Compton CC. The american joint committee on cancer: The 7th edition of the AJCC cancer staging manual and the future of TNM. Vol. 17, Annals of Surgical Oncology. 2010. p. 1471–4.

Zhao X, Wu Q, Gong X, Liu J, Ma Y. Osteosarcoma: a review of current and future therapeutic approaches. Vol. 20, BioMedical Engineering Online. BioMed Central Ltd; 2021.

Xu M, Wang Z, Yu X chun, Lin J hua, Hu Y cheng. Guideline for Limb-Salvage Treatment of Osteosarcoma. Orthop Surg. 2020 Aug 1;12(4):1021–9.

Levin AS, Arkader A, Morris CD. Reconstruction following tumor resections in skeletally immature patients. Vol. 25, Journal of the American Academy of Orthopaedic Surgeons. Lippincott Williams and Wilkins; 2017. p. 204–13.

Simpson E, Brown HL. Understanding osteosarcomas. J Am Acad Physician Assist. 2018 Aug 1;31(8):15–9.

Zhao J, Xu M, Zheng K, Yu X. Limb salvage surgery with joint preservation for malignant humeral bone tumors: Operative procedures and clinical application. BMC Surg. 2019 May 30;19(1).

Harrison DJ, Geller DS, Gill JD, Lewis VO, Gorlick R. Current and future therapeutic approaches for osteosarcoma. Vol. 18, Expert Review of Anticancer Therapy. Taylor and Francis Ltd; 2018. p. 39–50.

Erwin US, Cahyadi SD. Cryosurgery and vascularized fibular graft reconstruction in proximal tibia osteosarcoma in young children: A case report. Int J Surg Case Rep. 2021 Dec;89:106568.

Winkler K, Beron G, Delling G, Heise U, Kabisch H, Purfurst C, et al. Neoadjuvant Chemotherapy of Osteosarcoma: Results of a Randomized Cooperative Trial (COSS-82) With Salvage Chemotherapy Based on Histological Tumor Response. Vol. 6, J Clin Oncol. 1988.

Link MP, Goorin AM, Horowitz M, Meyer WH, Belasco J, Baker A, et al. Adjuvant chemotherapy of high-grade osteosarcoma of the extremity. Updated results of the Multi-Institutional Osteosarcoma Study. Clin Orthop Relat Res [Internet]. 1991 Sep;(270):8—14. Available from:

Li X, Zhang Y, Wan S, Li H, Li D, Xia J, et al. A comparative study between limb-salvage and amputation for treating osteosarcoma. Vol. 5, Journal of Bone Oncology. Elsevier GmbH; 2016. p. 15–21.

Whelan J, Seddon B, Perisoglou M. Management of Osteosarcoma. Curr Treat Options Oncol. 2006;7:444–55.

Zhang HD, Lu Z, Feng Y, Liu XL, Hou HM. [Experimental research in vitro of TK/GCV system for osteosarcoma MG-63 cell damage]. Zhongguo Gu Shang [Internet]. 2014;27(3):240–3. Available from:

Leinonen HM, Ruotsalainen AK, Määttä AM, Laitinen HM, Kuosmanen SM, Kansanen E, et al. Oxidative stress-regulated lentiviral TK/GCV gene therapy for lung cancer treatment. Cancer Res. 2012 Dec 1;72(23):6227–35.

Oryan A, Alidadi S, Moshiri A. Osteosarcoma: Current concepts, challenges and future directions [Internet]. 2015. Available from:

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