Comparative Experimental Studies of Calcium Channel Agonists and Antagonists against Ovariectomy Induced Osteoporosis In Rats

Background: Ca2+ channels and calcium signalling appears to play a critical role in the differentiation and functions of osteoclasts and osteoblasts and L-types voltage dependent calcium channels (VDCC) are expressed on bone cells. Either activation or blocking of these channels in bone homeostasis is found to be controversial. Based upon this we have compared effects of VDCC antagonist (-) Verapamil and VDCC agonist (+) Bay K-8644 against ovariectomy (OVX) induced bone loss in female Wister rats. Methods: Present study was designed as per the food and administration guidelines for ovariectomy rat model and test drug administration period was 40 days. At the end of the experiment various parameters were compared among the groups. Results: Among all the drugs calcium channel agonist CCA (+) Bay-K-8644 has shown protective effects by increase in the bone density, breaking strength and maintaining serum calcium, phosphorous and ALP level. Calcium channel blockers (CCB) (-) Verapamil has also offered protection in few parameters like bone length but not as good as Bay-K-8644. Conclusion: CCA (+) Bay-K-8644 has offered protection may be by reducing opening frequency, current amplitude of Cav 1.2 channels. Moreover it may have elevated cytosolic Ca2+ in osteoblast cells and decreases RANK-L induced osteoclast formation and bone resorption.