Treating Bone Quality in Chronic Kidney Disease

Abstract

While patients with chronic kidney disease (CKD) experience significant bone loss, little is known about the role of bone quality (properties independent of size and shape). Calcitriol is used to prevent bone loss by inhibiting parathyroid hormone (the main cause of bone breakdown in CKD), yet its impact on bone quality is unknown. Raloxifene improves bone quality, but its effects in CKD are unknown. This study examined the hypothesis that bone quality is deteriorated in CKD and that raloxifene but not calcitriol would improve bone quality. Using a rat model of CKD, mechanical properties of the tibia were assessed by nanoindentation, and composition was assessed by Raman spectroscopy. Animals with CKD were not different from normal controls with regard to elastic modulus, hardness, mineral‐to‐matrix ratio, or mineral crystallinity. Calcitriol treatment resulted in a higher mineral‐to‐matrix ratio (+20%), but it did not improve mechanics. Raloxifene, on the other hand, did not impact bone composition but led to substantially higher tissue hardness (+82%), consistent with previous data showing a mechanical effect independent of changes in tissue composition or bone mass. While animals with CKD may not have significant defects in bone quality at this stage of disease, these results indicate that improving the quality of the remaining tissue may be an effective means to compensate for bone loss in CKD. Nanoindentation Raman Spectroscopy Hardness (MPa) Elastic Modulus (GPa) Mineral‐to‐Matrix Ratio Mineral Crystallinity Normal (n=8) 196.97 +/‐ 23.53 11.13 +/‐ 2.57 2.69 +/‐ 0.44 0.053 +/‐ 0.0009 Chronic Kidney Disease ‐ No Treatment (n=9) 212.15 +/‐ 52.79 10.63 +/‐ 1.66 2.30 +/‐ 0.48 0.054 +/‐ 0.0008 Chronic Kidney Disease ‐ Calcitriol (n=11) 209.43 +/‐ 47.29 9.99 +/‐ 2.51 2.76 +/‐ 0.36 (*) 0.053 +/‐ 0.0004 Chronic Kidney Disease ‐ Raloxifene (n=10) 386.84 +/‐ 282.29 (*) 12.64 +/‐ 3.31 2.29 +/‐ 0.45 0.053 +/‐ 0.0005