[3] Many patients first complain of pain that may be worse at night, may be intermittent and of varying intensity and may have been occurring for a long time.

[citation needed] Several research groups are investigating cancer stem cells and their potential to cause tumors along with genes and proteins causative in different phenotypes.

[17] Most of the research involved counting number of osteosarcoma patients cases in particular areas which has difference concentrations of fluoride in drinking water.

The result is that the median fluoride concentrations in bone samples of osteosarcoma patients and tumor controls are not significantly different.

[citation needed] Microscopically: The characteristic feature of osteosarcoma is presence of osteoid (bone formation) within the tumor.

These cells produce osteoid describing irregular trabeculae (amorphous, eosinophilic/pink) with or without central calcification (hematoxylinophilic/blue, granular)—tumor bone.

Some characteristics of osteosarcoma on X-rays are sunburst appearance and Codman triangle (elevation of bony cortex by the tumour that caused new bone formation).

Even though radiographic findings for this cancer vary greatly, one usually sees a symmetrical widening of the periodontal ligament space.

A dentist who has reason to suspect osteosarcoma or another underlying disorder would then refer the patient to an Oral & Maxillofacial surgeon for biopsy.

It may also metastasise to the lungs, mainly appearing on the chest X-ray as solitary or multiple round nodules most common at the lower regions.

[citation needed] [24] A complete radical, surgical, en bloc resection of the cancer, is the treatment of choice in osteosarcoma.

[citation needed] Standard therapy is a combination of limb-salvage orthopedic surgery when possible (or amputation in some cases) and a combination of high-dose methotrexate with leucovorin rescue, intra-arterial cisplatin, adriamycin, ifosfamide with mesna, BCD (bleomycin, cyclophosphamide, dactinomycin), etoposide, and muramyl tripeptide.

The best reported 10-year survival rate is 92%; the protocol used is an aggressive intra-arterial regimen that individualizes therapy based on arteriographic response.

[2] It originates more frequently in the metaphyseal region of tubular long bones, with 42% occurring in the femur, 19% in the tibia, and 10% in the humerus.

[32] Osteosarcoma is the most common bone tumor in dogs and typically affects middle-aged large and giant breed dogs such as Irish Wolfhounds, Greyhounds, German Shepherds, Rottweilers, mountain breeds (Great Pyrenees, St. Bernard, Leonberger, Newfoundland), Doberman Pinschers and Great Danes.

[40] Canine osteosarcoma shows similar patterns of molecular somatic alterations to the human disease.

Both are characterized by genetic instability and karyotypic complexity and genes that are recurrently altered include TP53, RB1, PTEN, MYC, PIK3CA[41].

In contrast, mutations in the histone methyltransferase gene SETD2 are rare in human osteosarcoma, but have been identified in 21% of canine tumors.

[42] Osteosarcoma is also the most common bone tumor in cats, although not as frequently encountered, and most typically affect the rear legs.

[37] An 2020 study, published in The Lancet Oncology, reports the first confirmed case of osteosarcoma in a dinosaur, a Centrosaurus apertus from the Late Cretaceous, about 77 to 75.5 million years ago.

This study establishes that bone cancers, such as osteosarcoma, have deep roots in the evolutionary history of vertebrates.