This is the first report of international osteosarcoma incidence in subjects of all ages to our knowledge. The recent study of incidence and survival patterns in the U.S. found that osteosarcoma incidence, time-trends, survival, pathologic subtype, and anatomic site were varying among children and adolescents, middle ages, and elderly persons.8
This suggested that there may be important osteosarcoma incidence differences in these age groups throughout the world.
In individuals ≤24 years, the incidence rates were minimally variable between countries. Previously, a higher incidence of childhood osteosarcoma was reported in Southern Europe,15
particularly in Italy.5
We also found a slightly higher incidence in Italy (males: 5.3, females: 4.5) for ages 0–24, particularly for males in Florence and Torino. However, the highest rates were in Latin America (males: 7.0–7.6, females: 3.5–4.9). Rates were particularly high in all age groups in the Philippines and Ecuador. A high incidence of osteosarcoma has been observed in an earlier report in two African countries, Sudan and Uganda, compared to the relative frequency in populations of European origin.14
This is consistent with the finding that young and middle aged individuals of African American descent in the US had higher rates of osteosarcoma than whites.8
It is important to note that other differences between ethnic groups may be observed, but data are less complete in those populations
The earlier world-wide incidence peak observed in adolescent girls compared to boys links osteosarcoma to bone growth and an earlier occurrence of the adolescent growth spurt in girls, supporting the idea that bone growth and/or hormonal changes during puberty may have a role in osteosarcoma pathogenesis.21–23
The observation that the vast majority of adolescent tumors develop in the long bone epiphyses of the lower limbs1, 8, 24, 25
lends further support to this hypothesis.
An interesting difference between the age groups is the overall 1:1 male-to-female ratio of osteosarcoma cases in the elderly compared to the younger age groups male predominance (ages ≤24, 1.43:1; ages 25–59, 1.28:1). In the U.S. using SEER incidence data, osteosarcoma in the elderly was found to occur slightly less commonly in males than females (0.9:1).8
The rates were strikingly high for elderly male patients in the U.K. (particularly in the North Western and Oxford Regions), Australia, and Canada, to our knowledge the first time this has been reported. The interpretation of data from some Asian and Latin American countries was limited because some of these rates are based on less than 10 cases and may be unstable. Rates were not available for each elderly age stratum in these two regions, so it was difficult to determine an incidence peak in the elderly; interestingly, numbers of cases reported and the overall rates were comparatively lower in these regions.
The greater geographic variation observed in elderly patients could be due to several reasons: (1) diagnosis and/or classification differences among countries; (2) differences in completeness of cancer registration; (3) differences in environmental exposures that could alter risk of primary osteosarcoma; (4) exposures, such as irradiation, that could increase the chance of secondary osteosarcoma; and/or (5) different genetic components to osteosarcoma in the elderly, such as Paget’s disease.26
In elderly patients, osteosarcoma is often considered a secondary neoplasm attributed to the sarcomatous transformation of Paget’s disease of bone.27, 28
We were unable to separate osteosarcomas occurring with Paget’s disease from those that did not with this database. There is marked geographic variation observed in the prevalence of Paget’s disease, with a high prevalence noted in the UK, Australia, and North America, and lower levels in Asia and the Middle East.29, 30
which is similar to the high and low regions of elderly osteosarcoma incidence.
Competing risks due to different environmental and/or genetic risk factors could also be involved in the geographic variation observed in the elderly patients. For example, osteosarcoma in this age group may occur in body sites that have been previously irradiated for a different cancer,27, 28, 31
a variable that we were unable to assess. Differences based on geographic location in access to radiotherapy and other cancer treatment modalities could also exist which would affect the rates of secondary osteosarcoma..
It is theoretically possible that vitamin D deficiency could contribute to risk of osteosarcoma since vitamin D is required for bone development and vitamin D deficiency has been associated with risk of developing colon, prostate, breast, and several other cancers.32, 33
Vitamin D deficiency is recognized as pandemic34–38
and the elderly may be particularly affected.37, 39
One could also speculate that the increased rates in subjects of African descent are related to differences in vitamin D absorption. This hypothesis in osteosarcoma susceptibility has yet to be tested.
It is difficult to compare international survival rates for osteosarcoma because there are few estimates in the literature, few available data sources for older persons, and time frames have been reported differently. However, data from the Automated Childhood Cancer Information System (ACCIS; for ages 0–19 from 1993–1997)40
and the Eurocare-3 Study: Survival of Cancer Patients in Europe (for ages 0–14 from 1990–1994)41, 42
show that the 5-year survival rates for children and adolescents are similar in most European countries (55–75%), except for lower rates observed in Slovakia (19–20%), Estonia (26%), and Denmark (39%). Similar 5-year survival rates have also been observed in the U.S. (62%, ages 0–24; 68%, ages 0–14)8, 43
and Japan (51%, ages 0–14).44
The lower survival rates observed in Estonia, Slovakia, and Denmark could be a consequence of limited access to early diagnosis and appropriate treatment.43
The 5-year osteosarcoma survival rates in the U.S.8
increased significantly from the 1970s to the 1980s (U.S.: 51 to 63%; Japan: 18 to 51%), but have not improved further since the 1980s to the 1990s in the U.S.8
and Europe.42, 45
This lack of improvement during the last decade indicates an international need for more efficient management and new treatment strategies.
In summary, worldwide osteosarcoma incidence rates varied most in the elderly, with little geographic variation among the younger age groups. These data illustrate the importance of separating osteosarcoma incidence data by these age groups and inclusion of this information in more studies and databases.