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Although experimental and clinical evidence suggest that endogenous sex hormones influence bone sarcoma genesis, the hypothesis has not been adequately tested in an appropriate animal model. We conducted a historical cohort study of Rottweiler dogs because they frequently undergo elective gonadectomy and spontaneously develop appendicular bone sarcomas, which mimic the biological behavior of the osteosarcomas that affect children and adolescents.
Data were collected by questionnaire from owners of 683 Rottweiler dogs living in North America. To determine whether there was an association between endogenous sex hormones and risk of bone sarcoma, relative risk (RR) of incidence rates and hazard ratios for bone sarcoma were calculated for dogs subdivided on the basis of lifetime gonadal hormone exposure.
Bone sarcoma was diagnosed in 12.6% of dogs in this cohort during 71,004 dog-months follow-up. Risk for bone sarcoma was significantly influenced by age at gonadectomy. Male and female dogs that underwent gonadectomy before 1 year of age had an approximate one in four lifetime risk for bone sarcoma and were significantly more likely to develop bone sarcoma than dogs that were sexually intact [RR Â±95% CI = 3.8 (1.5â€“9.2) for males; RR Â±95% CI = 3.1 (1.1â€“8.3) for females]. Ï‡2 test for trend showed a highly significant inverse dose-response relationship between duration of lifetime gonadal exposure and incidence rate of bone sarcoma (P = 0.008 for males, P = 0.006 for females). This association was independent of adult height or body weight. We conclude that the subset of Rottweiler dogs that undergo early gonadectomy represent a unique, highly accessible target population to further study the gene:environment interactions that determine bone sarcoma risk and to test whether interventions can inhibit the spontaneous development of bone sarcoma.
Our finding that neutered Rottweiler dogs are at increased risk for bone sarcoma is consistent with the findings of Ru et al. (17) . Using a computerized database from North American Veterinary Teaching Hospitals from 1980 to 1994, a case-control study of 3062 osteosarcoma cases and 3959 control dogs was conducted to evaluate risk factors of osteosarcoma in purebred dogs of various breeds. Neutered dogs were at 2.2 times (95% CI = 2.0â€“2.4) greater risk of osteosarcoma than sexually intact dogs (17) . Because the database used in that study provided no information on age at gonadectomy, the study could not evaluate bone sarcoma risk in terms of duration of gonadal hormone exposure. Our results indicate that dogs undergoing early gonadectomy have the highest risk for bone sarcoma development….
In summary, this study found that male and female Rottweilers with the shortest lifetime gonadal exposure had the highest risk for bone sarcoma. Dogs that underwent early elective gonadectomy had a one in four lifetime risk of bone sarcoma development compared with a significantly reduced risk among dogs that were sexually intact throughout their lifetime.<