SAT-731 Impact of Maternal Roux-en-Y Gastric Bypass (RYGB) Surgery on Offspring Growth and Bone Health in Non-Human Primates (NHP)

Abstract Disclosure: K.A. Sauter: None. D.L. Takahashi: None. H. Blomenkamp: None. M. Shallman: None. C. Mcguire: None. C. McArthur: None. M.A. Kirigiti: None. J. Lo: None. R.T. Turner: None. U.T. Iwaniec: None. P. Kievit: None. Background: Obesity in women of reproductive age is increasing and is associated with adverse pregnancy outcomes. Surgical weight loss interventions, like RYGB, are utilized for the effective treatment of morbid obesity and its associated comorbidities pre-conception. However, RYGB is malabsorptive which can lead to micronutrient deficiencies that can potentially impact offspring outcomes such as healthy bone formation. Cases of Metabolic Bone Disease of Infancy have been reported in infants born to women who had previously undergone bariatric surgery. We developed a novel diet-induced obese rhesus macaque model of RYGB to determine the impact RYGB may have on offspring development, specifically bone health. Methods: Three cohorts of adult female macaques (n=10 each) were established to generate 6-month-old offspring: high fat diet (HFD) obese animals that underwent RYGB surgery, HFD obese animals, and lean control animals. Once RYGB females were weight stable, all females underwent timed mating breeding. To minimize maternal malnutrition post metabolic surgery, females received daily calcium and multivitamin supplementation. The dams produced 27 live offspring (n=8-10/cohort). Offspring were sent to necropsy at 6-months of age. Results: Post RYGB females were not deficient in vitamin B12, folate, ferritin, vitamin D or calcium throughout pregnancy. In utero, there were no significant differences in femur length, measured by ultrasound at gestational ages 65, 85, 135 and 155. Infants weighed at 1-week of age demonstrated no significant differences between cohorts. Interestingly, infants born to post RYGB mothers had significantly increased growth rate starting at 1-month of age versus control infants, which persisted until 6-months of age. At 5.5-months of age, post RYGB infants demonstrated greater lean and fat mass while no significant differences were observed in bone mineral content and density as measured by DEXA. Detailed micro-computed tomography (μCT) analysis of bone specimens from the axial (lumbar vertebra) and appendicular (femur) skeleton showed no discernable changes in cortical and cancellous bone microarchitecture. Additionally, circulating biochemical markers of bone resorption (C-terminal telopeptide of type 1 collagen (CTX)) and turnover (osteocalcin) demonstrated no differences between cohorts. Conclusion: This study investigated the possibility of altered bone growth/microarchitecture in offspring as a result of maternal RYGB prior to pregnancy. Pregnant females demonstrated circulating levels of vitamins and minerals within the suggested range for human pregnancies. Therefore, bone health in NHP offspring may be unaffected as proper maternal supplementation appeared sufficient. This study outcome suggests that maternal malnutrition, and not RYGB per se, could significantly contribute to cases of Metabolic Bone Disease of Infancy. Presentation: Saturday, July 12, 2025