Skeletal and body composition effects of orchiectomy in a colony of diet-induced obese cynomolgus macaques.

Obesity is a leading cause of secondary hypogonadism or low testosterone. Conversely, hypogonadism frequently leads to excess body fat/obesity demonstrating a potentially reciprocal relationship between the two. This study describes the impact of bilateral orchiectomy (ORX) in a colony of diet-induced obese (DIO) male Mauritius cynomolgus macaques (DIO-CM) maintained on a Western Style Diet (WSD). Body composition analysis via DXA was performed prior and up to 15 m postsurgery to determine the long-term changes in hypogonadism. As expected, ORX significantly reduced testosterone, inhibin B, and estrogen while increasing follicle-stimulating hormone and luteinizing hormone throughout the entire follow-up period. Animals lost significant body weight mainly due to a loss of lean but not fat mass. Orchiectomy had detrimental and long-lasting, 15 m postsurgery, effects on bone, including decreased total BMC and BMD, with the most drastic losses localized to the pelvic region. Additionally, animals demonstrated a transient elevation of numerous bone turnover markers. This model demonstrates that in a phenotypically well-characterized colony of DIO-CM, hypogonadism induces lean mass loss, increased body fat percentage, and numerous hallmarks of osteoporosis. This nonhuman primate model is relevant to human bone biology, age-related body composition changes, such as sarcopenic obesity, and hypogonadism and therefore could be utilized to test muscle and bone mass preserving interventions in the future.