Bisphenol A diglycidyl ether (BADGE), a PPARγ2 antagonist, has been shown to inhibit marrow adipogenesis and promotes bone formation in intact animals. We investigated the impact of BADGE on a new and more clinically relevant physiological model, the ovariectomized (OVX) rat model. Forty female Wistar rats were divided into four treatment groups (n=10/group): sham+vehicle, sham+BADGE, OVX+vehicle and OVX+BADGE for 12 weeks. Postmortem analyses included MRI, micro-CT, serological test, histomorphometry, biomechanical tests, RT-PCR and western blot. Overall, OVX induced a sequential marrow fat expansion accompanied by bone deterioration. Compared with OVX controls, BADGE reduced fat fraction of the distal femur by 36.3%, adipocyte density by 33.0%, adipocyte size by 28.6%, adipocyte volume percentage by 57.8%, adipogenic markers PPARγ2 and C/EBP by 50% in OVX rats. Similar results were observed in sham rats vs vehicle. BADGE could promote bone quality in sham rats; however, BADGE did not significantly improve trabecular microarchitecture, biomechanical strength and dynamic histomorphometric parameters except for trabecular separation in OVX rats. We concluded that early BADGE treatment at a dose of 30mg/kg attenuates marrow adiposity in ovary-intact and OVX rats, and stimulates bone formation in ovary-intact rats, but does not significantly rescue bone quality in OVX rats.
- Marrow fat
- PPARγ2 antagonist
- Copyright © 2016, American Journal of Physiology-Endocrinology and Metabolism