Reducing parathyroid hormone is essential for correcting cortical bone deficiencies associated with chronic kidney disease

Abstract

Chronic kidney disease (CKD) results in an increased fracture risk, partially due to elevations in parathyroid hormone (PTH). Bisphosphonates (BP's) reduce fracture risk by preventing bone loss, but the lack of data in CKD has limited their use. Using the BP zoledronic acid (ZOL) and calcium (CA) (known to lower PTH), the present study used a rat model of CKD to examine the impact of PTH levels on the skeletal abnormalities associated with kidney disease. Skeletally mature male rats with CKD (n=56) were given vehicle, ZOL, CA, or ZOL&CA for 10 weeks. Age‐matched male rats without CKD (n=14) served as controls. Outcomes were determined by serum PTH, femoral cortical porosity, and femoral mechanical testing. In untreated CKD animals, PTH levels were 12 times higher than in normal animals. Animals treated with CA and ZOL&CA had lower PTH values, whereas rats with ZOL alone did not. Compared to normal animals, untreated CKD rats had 41‐fold higher cortical porosity and lower bone strength (−31%). After correcting for differences in porosity, reductions in strength remained (−27%), indicating that CKD adversely impacts bone quality. Animals treated with CA and ZOL&CA had cortical porosity and bone strength similar to normal controls. ZOL alone did not alter porosity or strength relative to untreated CKD rats. These data indicate that normalization of PTH is necessary for controlling cortical bone abnormalities in CKD.Grant Funding Source: NIH