The effects of dantrolene and 2-aminoethoxydiphenyl borate (2-APB) on arsenic-induced osteoporosis.

Background: Arsenic can increase the risk of osteoporosis among the population in arsenic–endemic areas compared with the general population in non-endemic areas. And calcium overload is the related mechanisms of arsenic-induced osteoporosis However, there is a relative lack of clinical research on the treatment of arsenic-induced osteoporosis. Dantrolene and 2-APB, as Ca²⁺ influx inhibitor, can reduce calcium overload and play an important role in the excitation–contraction coupling of skeletal muscle. Therefore, we study the effects of dantrolene and 2-APB on arsenic-induced osteoporosis in this study. Objective: To study the effects of arsenic on the trabeculae of rats, and observe the effects of dantrolene and 2-aminoethoxydiphenyl borate (2-APB) on the trabeculae. Results: Compared with the control group, some indices of micro-CT (BV/TV, Tb.Th, Tb.N, BMD, and DA) and the alkaline phosphatase (ALP) activity of bone marrow stromal cells (BMSCs) decreased, while some indices of micro-CT (Tb.Sp, Tb.Pf, and SMI), biochemical indicators (ALT, AST, ALP, and GGT), and the Ca²⁺concentration of BMSCs increased in the Sodium arsenite (NaAsO₂) group (P < 0.05). Compared with the NaAsO₂ group, the indices of micro-CT and biochemical indicators improved, the Ca²⁺ concentration of BMSCs decreased, and the ALP activity of BMSCs increased in the dantrolene group, 2-APB group and dantrolene + 2-APB group (P < 0.05), especially dantrolene + 2-APB group. Conclusion: NaAsO₂ can lead to osteoporosis in rats, dantrolene and 2-APB can reduce the degree of arsenic-induced osteoporosis. [ABSTRACT FROM AUTHOR]