Abstract
Secondary hyperparathyroidism (SHPT) relates to high turnover bone loss and is responsible for most bone fractures among chronic kidney disease (CKD) patients. Changes in the Wingless/beta-catenin signaling (Wnt/β-catenin) pathway and Wnt inhibitors have been found to play a critical role in CKD related bone loss. A calcimimetic agent, cinacalcet, is widely used for SHPT and found to be similarly effective for parathyroidectomy clinically. A significant decrease in hip fracture rates is noted among US hemodialysis Medicare patients since 2004, which is probably related to the cinacalcet era. In our previous clinical study, it was proven that cinacalcet improved the bone mineral density (BMD) even among severe SHPT patients. In this study, the influence of cinacalcet use on bone mass among CKD mice was determined. Cinacalcet significantly reduced the cortical porosity in femoral bones of treated CKD mice. It also improved the whole-bone structural properties through increased stiffness and maximum load. Cinacalcet increased femoral bone wingless 10b (Wnt10b) expression in CKD mice. In vitro studies revealed that cinacalcet decreased osteoclast bone resorption and increased Wnt 10b release from osteoclasts. Cinacalcet increased bone mineralization when culturing the osteoblasts with cinacalcet treated osteoclast supernatant. In conclusion, cinacalcet increased bone quantity and quality in CKD mice, probably through increased bone mineralization related with osteoclast Wnt 10b secretion.
Highlights
Secondary hyperparathyroidism (SHPT) is the most common complication of chronic kidney disease (CKD) patients and plays a critical role in renal osteodystrophy (ROD) and cardiovascular disorders [1,2,3]
Increased bone resorption is noted with elevated bone marrow fibrosis and generalized bone loss [4,5,6,7]
SHPT patients have been found to have progressive cortical thinning and increased cortical porosity [12,13], which results in decreased cortical bone mineral density (BMD) [14]
Summary
Secondary hyperparathyroidism (SHPT) is the most common complication of chronic kidney disease (CKD) patients and plays a critical role in renal osteodystrophy (ROD) and cardiovascular disorders [1,2,3]. Increased bone resorption is noted with elevated bone marrow fibrosis and generalized bone loss [4,5,6,7]. The degree of mineralization is impaired in such patients because the recently formed bone is removed rapidly without adequate mineralization [9]. Bones formed from such a high turnover status have lower mineralization and trabecular micro-hardness than bones formed from normal or low turnover states [10,11]. SHPT patients have been found to have progressive cortical thinning and increased cortical porosity [12,13], which results in decreased cortical bone mineral density (BMD) [14]. SHPT is associated with both bone quantity and quality loss
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.
