Abstract
Osteocyte apoptosis is the first reaction to estrogen depletion, thereby stimulating osteoclastic bone resorption resulting in bone loss. We investigated the effects of two different risedronate (RIS) doses (high and low) on osteocyte apoptosis, osteoclast activity and bone loss in ovariectomized rats. Forty rats with ovariectomy (OVX) and sham ovariectomy (SHAM) were divided into 4 groups: 1) SHAM rats treated with saline (SHAM); 2) OVX rats treated with saline (OVX); 3) OVX rats treated with low-dose RIS (OVX-LR, 0.08 μg/kg/day); 4) OVX rats treated with high-dose RIS (OVX-HR, 0.8 μg/kg/day). All animals were sacrificed 90 days after surgery for the examinations of osteocyte apoptosis by caspase-3 staining, osteoclast activity by TRAP staining and bone volume by micro-CT scanning in lumbar vertebral cancellous bone. Both low and high dose RIS significantly reduced caspase-3 positive osteocytes, empty lacunae and TRAP positive osteoclasts in OVX rats. Although the difference in caspase-3 positive osteocytes was not significant between the OVX-LR and OVX-HR groups, numerically these cells were significantly more prevalent in OVX-HR (not OVX-LR) group than in SHAM group. TRAP positive osteoclasts were significantly higher in OVX-LR group than in SHAM or OVX-HR group. There was no significant difference in bone volume among the OVX-LR, OVX-HR and SHAM groups, but lower in OVX group alone. However, significant increase in trabecular thickness only occurred in OVX-LR group. We conclude that both low and high dose RIS significantly inhibit osteocyte apoptosis and osteoclast activity in OVX rats, but the low-dose RIS has weaker effect on osteoclast activity. However, low-dose RIS preserves cancellous bone mass and microarchitecture as well as high-dose RIS after estrogen depletion.
Highlights
The rats were divided into 4 groups of 10 rats each after surgery: 1) SHAM rats treated with saline as a vehicle; 2) OVX rats treated with saline as a vehicle; 3) OVX rats treated with low-dose RIS (OVX-LR); 4) OVX rats treated with high-dose RIS (OVX-HR)
Our study results demonstrated that both apoptotic osteocytes and empty lacunae in vertebral cancellous bone were significantly increased in OVX rats resulting in a severe decrease in normal osteocytes
Emerton et al [3] reported that osteocyte apoptosis was significantly increased in mice within 3 days after OVX, whereas osteoclastic bone resorption was increased in the regions concomitant with osteocyte apoptosis until 14 days after OVX
Summary
Estrogen depletion after menopause or ovariectomy (OVX) stimulates osteoclastic bone resorption, resulting in uncoupled bone remodeling in which the bone formed by osteoblasts. The anti-apoptotic effect on osteocytes is seen at much lower doses than that required for inhibiting osteoclast activity [16, 18]. Such dose-dependent effects are not so obvious in in vivo studies [17]. Low-dose BPs may have an effect against osteocyte apoptosis [16,17,18], it remains unclear if lowdose BPs can reduce bone resorption and preserve bone mass after estrogen depletion. The purposes of this study were to determine the low versus high dose (as defined) effects of RIS on osteocyte apoptosis, osteoclast activity and bone loss in rats after OVX
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
