Effects of Etelcalcetide on Bone Microstructure in the Adenine-Induced Chronic Kidney Disease Rat Model

Objective: Chronic kidney disease (CKD) with secondary hyperparathyroidism (SHPT) increases the risk of fragility fractures with deterioration of cortical and trabecular bone microstructure. Etelcalcetide (EC), which is used to treat SHPT, reduces parathyroid hormone (PTH) levels in the blood. However, the details of the effects of EC on the microstructure of cortical and trabecular bone remain unclear. This study investigated whether EC improved the cortical and trabecular bone microstructure in CKD model rats. Methods: Eight-week-old, male Wistar rats were fed with a 0.75% adenine diet for 4 weeks to establish the CDK model rats. At 20 weeks of age, the rats were divided into two groups (n = 9 - 11 in each group): CKD group (vehicle administration) and EC group (0.6 mg/kg, daily). EC was injected for 4 weeks starting at 20 weeks of age. After treatment, the biochemical tests, measurement of bone mineral density and bone strength, and evaluation of cortical and trabecular bone microstructure were performed. Results: Compared with the CKD group, the EC group showed significantly lower serum blood urea nitrogen, calcium, and inorganic phosphorus levels (p < 0.05 to p < 0.01), significantly higher cortical area, cortical volume, and cortical thickness (p < 0.05 to p < 0.01), and significantly lower cortical porosity (p < 0.01). In addition, the CKD group showed decreased bone strength in cortical bone, loss of bone mass in trabecular bone, and deterioration of bone structure, whereas these changes were suppressed in the EC group. Conclusions: EC significantly improved cortical microstructure and cortical porosity, suppressing deterioration of cortical bone strength and loss of trabecular bone in the adenine-induced CKD model rats.