Background

Roux-en-Y Gastric Bypass (RYGB) surgery has proven a valuable treatment option for morbid obesity, but also leads to metabolic bone disease. Sclerostin is a bone-secreted protein that has effects on both bone and glucose homeostasis. The effect of sclerostin antibody was assessed in a post-menopausal RYGB mouse model.

Methods

C57BL/6J female mice were fed a high-fat diet throughout the experiment. At age 17 weeks an ovariectomy was performed. At age 22 weeks, mice underwent either a sham or RYGB surgery. Then, mice received SostAb or Saline injections twice a week until sacrifice. Sham mice were body weight matched to RYGB mice. Glucose tolerance was assessed by intraperitoneal glucose tolerance test (IPGTT). Bone characteristics were analyzed 8 weeks after surgery.

Results

Fasting blood glucose levels were unchanged between groups. Glucose intolerance improved with SostAb in RYGB compared to saline injected mice, evidenced by a lower area under the curve (AUC) of blood glucose levels during IPGTT (-14000±3688mg/dL*120min, p<0.0001, n=7-9per group, mean±SEM). In contrast, it only slightly improved in Sham mice. µCT analysis of the tibia showed that SostAb in Sham mice lead to increased trabecular bone volume (BV/TV) (+3.8±0.6%, p<0.001) and cortical thickness (+0.05±0.003mm, p<0.0001), however after RYGB no increase was observed. Additionally, cortical porosity was increased strongly with SostAb after RYGB (+5±1%, p<0.001), while it did not increase with SostAb in Sham mice.

Conclusions

SostAb treatment after RYGB in postmenopausal mice led to an increased porosity. On the other hand, the treatment improved glucose tolerance.