Abstract
PURPOSE: It is clinically important to determine the efficacy of estrogen replacement for postmenopausal women combined with mobility difficulties, due to the potential risks of estradiol. The objective of the current study was to investigate the effect of estradiol replacement on osteoporosis induced by the ovariectomy (OVX) combined with unilateral sciatic neurectomy (SN) in a rat model. METHOD: Female Sprague-Dawley rats were subjected to OVX and unilateral SN on the right hindlimb (OVX+SN) or sham surgery (CTRL). 17β-estradiol (E2) or vehicle was administrated to the rats immediately, and followed by every other day. Bone mass and trabecular microarchitecture were analyzed using micro-Computed Tomography (micro-CT) and histology at days 3, 7, 14, and 28 post-surgery. The local expressions of sclerostin/SOST, secreted exclusively by osteocytes, and tartrate-resistant acid phosphatase 5b (TRAP 5b), produced mostly by osteoclasts, were examined by immunohistochemistry and TRAP staining, respectively. Serum markers of bone resorption, including C-terminal telopeptides of type I collagen (CTx), receptor activator for nuclear factor κB ligand (RANKL), and TRAP 5b, were quantified by enzyme linked immunosorbent assay (ELISA). RESULT: Based on micro-CT analysis, E2 treatment of OVX+SN rats improved the preservation of the bone volume fraction (BV/TV) and trabecular number (Tb.N) in the tibias at day 14 post-surgery, which were 43% and 46% higher in OVX+SN+E2 rats than those in OVX+SN rats, respectively. However, the impact of E2 was transient and disappeared at day 28. Expression of sclerostin in the tibias of OVX+SN rats was significantly elevated at day 7 post-surgery compared with the CTRL, but was suppressed until day 14 with E2 replacement. CONCLUSION: Our results showed that estrogen replacement could transiently protect against bone loss in OVX rats combined with mechanical unloading. The up-regulation of sclerostin expression appears to be transiently delayed by E2 treatment in our models.