Background

Bone loss is common after bariatric surgery. Sclerostin antibody is an effective treatment for osteoporosis. This study takes advantage of a well-designed animal model, aiming to uncover mechanisms underlying bone loss in this high-risk population.

Methods

Six ovariectomized mice, fed a high-fat diet (HFD) to induce obesity, received Roux-en-Y gastric bypass (RYGB) surgery. Seven ovariectomized HFD mice received sham surgery and served as control. Animals were sacrificed 8 weeks postoperatively. mRNA was extracted from the kidneys using TRIzol and qRT-PCR experiments were performed to quantify substrates associated with active vitamin D (1,25 dihydroxyvitamin D) formation and degradation, including CYP27B1, CYP 24, and TRPV5. Cortical and trabecular bone mass were assessed by micro computed tomography (mCT). A second study treated ovariectomized HFD mice that had RYGB or sham surgery with sclerostin antibody or carrier. Intraperitoneal glucose tolerance testing (IPGTT) was performed to assess glucose clearance. Statistical analyses were performed using unpaired two-tailed Student t-test; significance set at p<0.05.

Results

qRT-PCR analyses showed RYGB mice had a six-fold increase of renal CYP27B1 mRNA expression (p=0.0021) compared to sham mice (given arbitrary value, 1). CYP24 and TRPV5 did not show statistically significant changes compared to sham mice. IPGTT showed that RYGB mice injected with sclerostin antibody have improved clearance of glucose implying improved insulin sensitivity.

Conclusions

These findings may be helpful in guiding treatment for bariatric patients postoperatively. We aim to assess the impact of sclerostin antibody on insulin sensitivity using ELISA.